Contents lists available at ScienceDirect [604891]

Contents lists available at ScienceDirect
Trends in Food Science & Technology
journal homepage: www.elsevier.com/locate/tifs
Review
Biotechnological potential of yeasts in functional food industry
Amit Kumar Raia,∗, Ashok Pandeyb, Dinabandhu Sahooa,c,∗∗
aInstitute of Bioresources and Sustainable Development, Sikkim Centre, Tadong 737102, Sikkim, India
bCSIR-Indian Institute of Toxicology Research, Lucknow 226001, India
cInstitute of Bioresources and Sustainable Development, Imphal 795001, Manipur, India
ARTICLE INFO
Keywords:
YeastFunctional foods
Probiotics
PeptidesMetabolic engineeringABSTRACT
Background: Biotechnological potential of yeasts can be evidenced by the rich history of its application in food
fermentation. Several yeast species isolated from fermented foods have been characterised and applied as
starter/co-starter in functional food industries. The outcome of modern research in the recent past on nu-traceuticals and development of functional foods using yeasts suggests its bright future in food biotechnology.Scope and approach: In this article, bioactive compounds produced using yeasts including β-glucan, carotenoids,
glutathione, bioactive peptides, γ-aminobutyric acid, organic selenium, prebiotic oligosaccharides and free
polyphenols, are discussed. Yeast species having probiotic potential as well as therapeutic properties are high-lighted in the manuscript. Recent studies on metabolic engineering approaches applied to develop yeast strains
with additional functional properties with higher industrial importance have also been reviewed.
Key Findings and Conclusions: The current review summarizes the importance of yeast in the production of
functional food and development of bioprocesses for the production of high value nutraceuticals. The review alsohighlights the importance of yeast as a single starter as well as a component of mixed starter cultures in pro-
duction of bioactive metabolites. However, there is a need of exploration of novel yeast strains that have theability to produce novel and efficient biocatalysts from traditional fermented foods for advances in food industry
bioprocesses.
1. Introduction
Yeasts are eukaryotic microorganisms that include a heterogenous
group of microbes representing the phyla Ascomycetes and
Basidiomycetes that have a biotechnological potential in the food in-
dustry. Yeast are responsible for the production of a wide range of
fermented products ranging from alcoholic beverages prepared using
different types of substrates, fermented milk products including cheese,
cereal based leavened products, and condiments ( Rai & Jeyaram,
2017 ). During the natural fermentation process, development of the
final product depends on the growth of either di fferent types of yeasts
or a mixed culture fermentation supported by lactic acid bacteria and
filamentous fungi ( Chaves-Lopez et al., 2014; Dung, Rombouts, & Nout,
2006 ;Liu & Tsao, 2009 ). Yeast plays several important roles during
food fermentation including alcohol production, production and utili-
zation of organic acids, improvement of flavour, aroma and texture,
enhancement of nutritional properties and reduction of anti-nutritionalfactors and toxins ( Chaves-Lopez et al., 2014 ;Rai & Jeyaram, 2017 ).
Yeast strains isolated and characterised from several naturallyfermented foods have been successfully applied as starter/co-starter forthe production of functional foods at industrial level.
Yeasts are responsible for the production of di fferent types of
functional foods and are key players in the production of nutraceuticals
(Padilla et al., 2015; Rai, Sanjukta, & Jeyaram, 2017 ;Rai & Jeyaram,
2017 ). Functional foods are conventional food products, which are
taken as a part of normal diet and demonstrate health bene fits beyond
their nutritional properties, whereas nutraceuticals constitute puri fied
food components that are proven to exhibit health bene fits. In fer-
mented food products, yeasts enhance bioactive components by theproduction of enzymes, metabolites or they act in a synergistic manner
along with other groups of microorganisms resulting in the improve-
ment of functional properties ( Rai, Kumari, Sanjukta, & Sahoo, 2016).
Yeasts have diverse applications in the functional food industry as (i)live cells that can be used as probiotics, (ii) cell wall constituents (such
asβ-glucan) having nutraceutical value, (iii) secreted extracellular
fractions consisting of bioactive metabolites (folate, carotenoids, γ-
amino butyric acid), and (iv) producers of speci fic enzymes responsible
for food metabolites biotransformation resulting in the production of
https://doi.org/10.1016/j.tifs.2018.11.016
Received 18 June 2018; Received in revised form 12 November 2018; Accepted 12 November 2018∗Corresponding author. Institute of Bioresources and Sustainable Development, Tadong, Sikkim, India.
∗∗Corresponding author. Institute of Bioresources and Sustainable Development, Imphal, Manipur, India.
E-mail addresses: amitraikvs@gmail.com ,amitrai.ibsd@gov.in (A.K. Rai), dbsahoo@hotmail.com (D. Sahoo).Trends in Food Science & Technology 83 (2019) 129–137
Available online 14 November 2018
0924-2244/ © 2018 Elsevier Ltd. All rights reserved.
T

high value nutraceuticals ( Padilla et al., 2015 ;Rai et al., 2016 ). Several
authors have reported speci fic enzyme producing yeasts, which help in
production of substrate-derived bioactive compounds such as peptides,
oligosaccharides and free polyphenols ( Chua, Lu, & Liu, 2017 ;Padilla
et al., 2015 ;Rai et al., 2016 ). In the recent past, metabolic engineering
has been applied to develop e fficient strains of yeast for the production
of oligosaccharides ( Han et al., 2017 ;Wang, Li, & Wang, 2016 ) and
bioactive compounds such as carotenoids ( Bhataya, Schmidt-Dannert, &
Lee, 2009 ), polyphenols ( Rodriguez et al., 2017 ) and folates ( Walkey,
Kitts, Liu, & Van Vuuren, 2015 ). Potential of yeasts and their enzymes
in production of di fferent types of nutraceuticals is presented in Fig. 1.
Owing to the potential of yeasts in food biotechnology, the current
review attempts to summarize the updated research on the role of
yeasts in production of functional foods and nutraceuticals.
2. Yeasts as probiotic agents
Probiotic microorganisms in the form of supplements or fermented
foods are used for the improvement of health and wellness of the host.
There are various qualities that are needed for a microorganism to be
characterised as a probiotic, which includes growth at low pH, ability to
tolerate bile, cell surface hydrophobicity and auto-aggregation ( Fadda,
Mossa, Deplano, Pisano, & Cosentino, 2017). Most of the studies onprobiotic microorganisms have been carried out in the bacterial system
but in recent past, yeast has also shown its potential as a probiotic
(Saber, Alipour, Faghfoori, Jam, & Khosroushahi, 2017a ,b). Yeast holds
several advantages in comparison to bacteria as they are approximately
ten times bigger than bacterial cells, normally resistant to antibiotics,
which are necessary for their resistance during antibiotic treatment,
and they have not been reported for transfer of genes related to anti-
biotic resistance.
Yeast species reported to possess probiotic properties includeSaccharomyces cerevisiae ,Kluyveromyces marxianus ,Kluyveromyces lactis ,
Debaryomyces hansenii ,Saccharomyces boulardii ,Torulaspora delbrueckii ,
Candida krusei, Yarrowia lipolytica, Pichia fermentase and Pichia ku-
driavzevii (Kumura, Tanoue, Tsukahara, Tanaka, & Shimazaki, 2004 ;
Saber et al., 2017a ,b).S. boulardii is an extensively studied yeast species
having several probiotic properties and has been used in many coun-
tries as a therapeutic and preventive agent ( Kelesidis & Pothoulakis,
2012 ). Further, S. boulardii is widely used as an economical and e ffi-
cient probiotic yeast against in flammatory bowel disease and for the
treatment of di fferent
types of diarrhoea in humans as well as animals
(Kelesidis & Pothoulakis, 2012; Romanin et al., 2015 ;Szajewska &
Kołodziej, 2015). A meta-analysis study on the e ffect of S. boulardii on
patients with antibiotic-associated diarrhoea concluded that S. boulardii
can be an e ffective probiotic agent for prevention of antibiotic-asso-
ciated diarrhoea in patients including adults as well as children
(Dinleyici, Kara, Ozen, & Vandenplas, 2014; Szajewska & Koł odziej,
2015 ).
Several researchers have screened yeast strains having probiotic
properties from fermented foods, resulting in selection of potentialyeast isolates with additional health promoting properties ( Aloglu,
Ozer, & Oner, 2016 ;Fadda et al., 2017 ;Romanin et al., 2015) Yeast
isolated from a wide range of fermented foods have also been screened
for probiotic e ffect and ability to assimilate cholesterol ( Aloglu et al.,
2016 ).K. marxianus CIDCA 8154, probiotic yeast was shown to possess
anti-in flammatory e ffect and the ability to reduce oxidative stress
(Romanin et al., 2015 ).S. cerevisiae ARDMC1 strain isolated from tra-
ditional rice beer starter cake has been shown to possess probiotic e ffect
as well as hypocholesterolemic activity in rat model ( Saikia et al.,
2017 ). Research in recent past has also shown that metabolites secreted
from probiotic yeasts also exhibit anticancer e ffect (Saber et al., 2017a ,
b). Probiotic metabolites secreted by P. kudriavzevii AS-12 were ex-
amined for anticancer activity and it was found that the yeast
Fig. 1. Role of yeast in production of functional food and development of bioprocess for producing important nutraceuticals. GOS –Galacto-oligosaccharides, FOS –
Fructooiligosaccharides, GABA –γ-aminobutyric acid.A.K. Rai et al. Trends in Food Science & Technology 83 (2019) 129–137
130

metabolites exhibited anticancer e ffect in colon cancer cells (HT-29 and
Caco-2) ( Saber et al., 2017a ). Similarly, metabolites produced by K.
marxianus AS41 isolated from dairy origin, having probiotic properties
showed pro-apoptotic action on epithelial cancer cells ( Saber, Alipour,
Faghfoori, & Khosroushahi, 2017b ). Pineapple juice fermented with
Meyerozyma caribbica isolated from pineapple resulted in the product
having improved probiotic and functional properties in comparison to
S. cerevisiae var. boulardii ( Amorim, Piccoli, & Duarte, 2018 ). In an-
other study, cereal mixed substrate fermented using Pichia Kudriavzevii
OG32, a probiotic strain, exhibited hypolipidaemic and antioxidant
effects in rats fed with high cholesterol diet ( Ogunremi, Sanni, &
Agrawal, 2015 ).
3. Yeast cells wall constituent as functional food ingredients
Yeast cells are a source of fibre,β-glucan, which is known to im-
prove the immune system, lower cholesterol levels in blood and ex-
hibited anti-in flammatory activity ( Vieira et al., 2016). The biochem-
ical composition of the cell wall of yeast varies among di fferent genus
and is dependant on growth conditions, which a ffects the functional
properties of the cell wall polysaccharide ( Galinari et al., 2017 ;Jaehrig
et al., 2008). Cell wall composition of S. cerevisiae suggests that its
comprises of β(1→3)-D-glucan (50 –55%), β(1→6)-D-glucan (5 –10%),
mannoprotein complex (35 –40%) along with chitin (2%) ( Kwiatkowski,
2009 ). Subsequently, Saccharomyces β-glucans –also referred as “yeast
beta-glucans ”was approved by the European Food Safety Authority
(EFSA) for its application as a novel food ingredient suggesting a con-centration limit ranging from 50 to 200 mg ( EFSA, 2011).
Cell wall of S. cerevisiae is an important source of β-glucan, which
has been shown to improve the functionality of food products ( Borchani
et al., 2016). (1 →3), (1→6)–D-glucan
isolated from cell wall fraction
ofS. cerevisiae showed reasonably good antioxidant activity ( Jaehrig,
Rohn, Kroh, Fleischer, & Kurz, 2007 ). Further, it was also shown that
difference in growth medium signi ficantly a ffects the glucan content in
the cell walls of S. cerevisiae (Jaehrig et al, 2007). β-glucans adminis-
tration to wistar rats receiving high fat diet resulted in lowering ofblood glucose (23.97%), triacylglycerols (16.77%) and total cholesterol
(13.33%) in comparison to the control group ( De Araujo et al., 2016 ).
β-glucans derived from cell wall of S. cerevisiae have been reported to
modulate immune response ( Pelizon, Kaneno, Soares, Meira, & Sartori,
2005 ) and enhance the INF- γproduction in BALB/c mice, suggesting its
potential in stimulating the immune system ( Javmen et al., 2015 ).
Mannan extracts from yeast cell wall of dried S. cerevisiae added to
yogurt increased the viability of probiotic bacteria after production ( Al-
Manhel & Niamah, 2017). Cell wall α-D mannan fraction from K.
marxianus CCT7735 exhibited antiproli firative and good antioxidant
activity, which was evident from reducing power potential, metalchelating and hydroxyl radical scavenging activities ( Galinari, Almeida-
Lima, Macedo, Mantovani, & Rocha, 2018 ). The cell wall fractions also
induced nitric oxide production and mitogenic activity in macrophages,
suggesting that the fractions had immunomodulatory e ffects. Cell wall
constituents of yeast in fermented foods are a potential source ofbioactive molecules providing functional properties to the product.
4. Bioactive metabolites from yeast having nutraceutical potential
Yeast is known for the production of several bioactive components
as nutraceuticals, which form an integral part of the functional food
industry including γ-aminobutyric acid (GABA), folate and carotenoids
(Chen et al., 2016; Greppi et al., 2017 ;Han & Lee, 2017 ). Yeast fer-
mented products have shown to possess several bioactive metabolitesresponsible for improving the functionality of the product ( Table 1 ).
Yeast has been reported for the production of GABA by decarboxylationreaction by the enzyme glutamate decarboxylase ( Han, Jeon, Lee, &
Lee, 2016 ;Han & Lee, 2017 ). Among 182 yeast strains, Sporobolomyces
carnicolor 402-JB-1 and Pichia silvicola UL6-1 were selected as potentialstrains for the production of γ-aminobutyric acid ( Han et al., 2016).
Recently, Han and Lee (2017) used P.
silvicola UL6-1 and S. carnicolor
402-JB-1 for the production of GABA, resulting in 139.4 μg/ml and
179.2 μg/ml yield, respectively. GABA production was also reported by
S. cerevisiae strain isolated from traditional Korean Bokbunja wine for
application in the production of functional wines enriched with GABA
(Song & Baik, 2014).
Folate is one of the essential cofactors in several biochemical reac-
tions and its de ficiency is becoming a common problem globally
(Korhola et al., 2014 ;Greppi et al., 2017 ). Fermentation using yeasts for
the development of functional foods, has resulted in folate rich fer-
mented foods and beverages ( Kariluoto et al., 2006; Hjortmo,
Hellstrom, & Andlid, 2008a ,b). Rye dough fermentation using baker's
yeast, S. cerevisiae ALKO 743 and three sourdough yeasts, S. cerevisiae
TS 146, Candida milleri CBS 8195, and Torulaspora delbrueckii TS 207
increased folate content from 15 to 23 μg/100 g ( Kariluoto et al., 2006).
Yeast isolates from Russian ke fir granules, belonging to genus Sac-
charomyces andCandida , were shown to produce high folate content in
the form of 5-formyltetrahydrofolate and 5-methyltetrahydrofolate(Patring et al., 2006). Folate production was reported in togwa , a fer-
mented maize based porridge prepared using Candida glabrata TY26
and S. cerevisiae TY08, which was higher in comparison to other yeast
strains ( Hjortmo et al., 2008a ). Folate content in white wheat bread
leavened using S. cerevisiae CBS7764 strain was found to enhance by
3–5 fold depending on culture conditions in comparison to bread lea-
vened with commercial baker's yeast ( Hjortmo, Patring, Jastrebova, &
Andlid, 2008b ). Among 65 strains of yeast isolated from barley kernel,
S. cerevisiae, R. glutinis ,Pseudozyma spp. and K. marxianus were found to
be best for folate production ( Korhola et al., 2014). Recently, probiotic
Pichia kudriavzevii strain was found to be a potential candidate for folate
production among 93 yeast isolates from cereal-based traditional foodof West Africa ( Greppi et al., 2017 ).
Carotenoids are natural pigmented bioactive compounds having a
potential application in the functional food industry as they are knownfor preventing oxidative stress –related diseases ( Chen et al., 2016;
Mannazzu,
Landolfo, & Buzzini, 2015 ). Yeasts species commonly known
for production of di fferent types of carotenoids include Phaffia rhodo-
zyma ,Rhodotorula spp., Rhodosporidium spp, Sporidiobolus spp. and
Sporobolomyces spp. ( Mannazzu et al., 2015 ). The major carotenoids
produced by yeast include astaxanthin, β-carotene, γ-carotene, torulene
and torularhodin ( Mannazzu et al., 2015; Moline, Libkind, & Van
Broock, 2012 ). Glutathione is a non protein thiol peptide having the
ability to reduce the adverse e ffect of reactive oxygen species, making it
one of the potential candidates for nutraceutical applications ( Musatti,
Manzoni, & Rollini, 2013; Liang, Du, & Chen, 2009 ).S. cerevisiae and
Candida utilis are the most widely studied yeasts and were reported to
produce glutathione ( Musatti et al., 2013 ;Liang et al., 2009). Inclusion
of yeast strains producing these bioactive metabolites in fermentedproducts is likely to have a positive impact on consumers.
5. Yeast in biotransformation for the production of high value
nutraceuticals
Production of enzymes during fermentation results in a wide range
of biochemical changes depending on its speci ficity to the substrate ( Rai
et al., 2017). The changes mediated by the enzymes are responsible for
(i) the hydrolysis of the complex substrate to a simpler form, and (ii)
transformation of a biomolecule into its highly bioactive form. The
outcome of the biochemical change depends on the microorganism used
for fermentation at the strain level and the biochemical composition ofthe substrate ( Rai et al., 2017 ). Interaction of yeast and food compo-
nents results in the release of di fferent type of metabolites, exhibiting
specific health bene fits depending on the biochemical composition of
the product. The metabolites reported in yeast fermented foods andproduced by yeast dependent bioprocess include biologically active
peptides, free polyphenols and bioactive oligosaccharides ( Rai &A.K. Rai et al. Trends in Food Science & Technology 83 (2019) 129–137
131

Jeyaram, 2017).
5.1. Enhancement of polyphenols during fermentation
Yeasts are good producers of β-glucosidase, which is responsible for
the transformation of bound polyphenols (glycosides) to free form
(aglycone), improving their bioactivity in a wide range of fermented
foods and beverages ( Gaensly, Agustini, Silva, & Picheth, 2015; Rai &
Jeyaram, 2017 ). Yeast plays an important role in increasing the poly-
phenol content of cereal products by degradation of bound and con-
jugated phenolic acids to their free form ( Ogunremi et al., 2015 ).
Soybean extract fermented with S. cerevisiae resulted in higher poly-
phenol and flavanoid content resulting in an increase in DPPH radical
scavenging activity and reducing power potential ( Romero, Doval,
Sturla, & Judis, 2004). Enhancement of antioxidant properties in okara
fermented using Yarrowia lipolytica was also due to increase in poly-
phenol content ( Vong, Au Yang, & Liu, 2016 ).
In fermented alcoholic beverages, the health bene fits of the product
are dependent on factors such as polyphenols and alcohol content ( Rai
& Jeyaram, 2017). Changes in polyphenol content and their antioxidantactivities during fermentation have been studied in several alcoholic
beverages ( Heinonen, Lehtonen, & Hopla, 1998; Rai & Appaiah, 2014;
Rai & Jeyaram, 2017 ). Resveratrol, a polyphenol responsible for several
health bene fits was found to increase up to 102% during alcoholic
fermentation of grape must using β-glucosidase producing yeast strains,
without modifying its biochemical composition and sensory properties
(Gaensly et al., 2015 ). Increase in polyphenol content and antioxidant
activity in a dose dependent manner has been observed in a low alco-holic Garcinia beverage fermented using di fferent yeast species ( Rai &
Appaiah, 2014 ). Analysis of polyphenol levels of 44 berry and fruit
wines showed that the content of total polyphenols ranged from 91 to
1820 mg gallic acid equivalents/litre with good antioxidant properties
(Heinonen et al., 1998 ). Moderate consumption of wine can have a
therapeutic e ffect by preventing several diseases associated with oxi-
dative stress such as cancer and diabetes, inhibit platelet aggregation,
lower blood pressure, prevent LDL oxidation and have a bene ficial ef-
fect in other cardiovascular disorders, neurological diseases and os-teoporosis ( Rai & Jeyaram, 2017 ).
Traditionally prepared Chinese rice wine also claims to possess
health promoting properties and has been used to prevent cancer,ageing and cardiovascular diseases ( Que, Mao, & Pan, 2006; Rai &
Jeyaram, 2017 ). Rice wines have shown enhanced levels of poly-
phenols, which also correlated with high free radical scavenging ac-
tivity, reducing power potential and total antioxidant activity ( Queet al., 2006 ). Among five different Chinese rice wines analysed, nuomi
had the highest level of phenolic acid content resulting in higher anti-oxidant
activity, whereas Foshou had low phenolic acid levels resulting
in low activity ( Que et al., 2006 ).Haria, a rice based fermented alco-
holic beverage consumed in India, has also shown to exhibit reasonably
good radical scavenging activity ( Ghosh et al., 2015). In a recent study,
soya whey was fermented into soy alcoholic beverage using S. cerevisiae
commercial strains, which resulted in enrichment with free iso flavones
formed on hydrolysis of iso flavone glucosides into iso flavone aglycone
(Chua et al., 2017 ). Fermented pineapple beverage prepared using M.
caribbica inoculum, resulted in the product having high total phenolic
compounds (196.93 mg/L), ferulic acid (33.2 mg/L), chlorogenic acid
(3.64 mg/L), vanillin (0.18 mg/L) and catechin (155.56 mg/L) ( Amorim
et al., 2018 ).
5.2. Yeast in production of oligosaccharides
Fermentation of carbohydrate rich substrates using yeasts that have
the ability to produce speci fic carbohydrate modifying enzymes results
in the production of bioactive oligosaccharides ( Maugeri &
Hernalsteens, 2007 ;Padilla et al., 2015; Rodriguez-Colinas et al.,
2011 ). Lactulose oligosaccharides were produced using β-galactosi-
dases from K. marxianus and K. lactis isolated from dairy sources by
isomerisation reaction of transgalactosylated cheese whey permeate(Padilla et al., 2015 ). The products of transgalactosylated cheese whey
permeate contained prebiotic carbohydrates such as lactulose, oligo-saccharide derived from lactulose (OsLu), tagatose and galacto-oligo-
saccharides. Further, the amount of galacto-oligosaccharides produced
by cheese manufacturing by-products was comparable to the yield
when pure lactose was used as the substrate. Prebiotic galacto-oligo-
saccharides production from lactose has also been reported using β-
galactosidases producing K. lactis CECT1931 strain ( Rodriguez-Colinas
et al., 2011 ); and fermentation using Pseudozyma tsukubaensis and Pi-
chia kluyveri (Fai, Simiqueli, Ghiselli, & Pastore, 2015). In another
study, K. lactis was used during both synthesis as well as puri fication
step for the production of galactooligosaccharides (purity > 95%)(Sun et al., 2016 ).
Screening of yeast strains with high fructosyl transferase activity
resulted in discovery of three potential strains, Candida sp LEB-I3,
Cryptococcus sp. LEB-V2 and Rhodotorula sp. Moreover, the LEB-U5
stain was able to produce fructo-oligosaccharides from sucrose(Maugeri & Hernalsteens, 2007). High content of fructo-oligosacchar-
ides was also produced by successive fermentation of sucrose usingyeasts
stains including Aureobasidium pullulans andS. cerevisiae (NobreTable 1
Selected functional fermented products using yeast and their functional properties.
Products Yeast species Functional properties References
White wheat bread S. cerevisiae CBS7764 Folate content enhanced by 3 –5 fold Hjortmo et al. (2008b)
Maize based porridge Candida glabrata TY26 and S. cerevisiae TY08 Enhancement of Folate level. Hjortmo et al. (2008a)
Pearl millet fermented gruel Pichia kudriavzevii Probiotic and enhancement of folate
contentGreppi et al. (2017)
Bioactive protein hydrolysate S. cerevisiae Bioactive hydrolysate havingantioxidant propertyRai et al. (2016)
Fermented pineapple
beverageM. caribbica Probiotic properties Amorim et al. (2018)
Fermented Garcinia beverage S. cerevisiae, Hanseniaspora sp. (Accession no. U826968 ) Increase in antioxidant properties Rai & Appaiah, 2014
Rye dough fermentation S. cerevisiae ALKO 743, S. cerevisiae TS 146, Candida milleri CBS
8195, Torulaspora delbrueckii TS 207Enhancement of Folate level(15 –23μg/100 g).Kariluoto et al. (2006)
Soy alcoholic beverage S. cerevisiae Enhancement of iso flavone content Chua et al. (2017)
Fermented cereal-mix Pichia kudriavzevii OG32 Hypolipidaemic, probiotic and
antioxidant e ffectsOgunremi et al. (2015)
Fermented brown rice flour baker's yeast (Eagle QS6540 2801 0001, China) Increased phenolics and antioxidants Ilowefah, Bakar, Ghazali, Mediani,& Muhammad, 2014
White wine S. cerevisiae and Saccharomyces bayanus Increase in selenomethionine Perez-Corona et al. (2011)
Selenium enriched beer S. cerevisiae andSaccharomyces uvarum Increase in selenomethionine Sanchez-Martrinez et al., 2012
Bioyogurt from Bu ffalo milk S. cerevisiae Prebiotic (yeast mannan extract) Al-Manhel and Niamah (2017)A.K. Rai et al.
Trends in Food Science & Technology 83 (2019) 129–137
132

et al., 2016 ). Prebiotic isomalto-oligosaccharides were produced using
maltose as a substrate by the application of α-glucosidase from yeast
Xantophyllomyces dendrorhous (Fernández-Arrojo et al., 2007 ). Lactu-
lose oligosaccharides, isomalto-oligosaccharides, galacto-oligosacchar-
ides and fructo-oligosaccharides are well known for their prebiotic
properties.
5.3. Yeast in production of bioactive peptides
Yeasts associated with protein rich fermented foods possess dif-
ferent types of proteases and peptidases, which are accountable for
breakdown of the proteins to small peptides and further into free amino
acids ( Li, Sadiq, Liu, Chen, & He, 2015 ;Rai & Jeyaram, 2017 ). Bioactive
peptides are produced upon breakdown of protein rich food by theaction of proteolytic yeasts that are dominant during fermentation
(Chaves-Lopez et al., 2012 ). Depending on size of the peptide, apart
from the sequence and composition of amino acids, it can exhibit sev-eral health bene fits such as antioxidant, antihypertension, im-
munomodulatory, antimicrobial and cholesterol lowering properties(Rai et al., 2017 ). In recent years, proteolytic yeast strains have been
studied for the production of protein hydrolysates and peptides, whichcan produce functional food and nutraceuticals ( Chaves-Lopez et al.,
2012 ;Rai et al., 2016 ;Rai & Jeyaram, 2017). Antioxidant properties of
a peptide are dependent on the existence of hydrophobic and aromatic
amino acids (tryptophan, histidine and phenylalanine) ( Pownall,
Udenigwe, & Aluko, 2010 ). In a recent study, yeast isolated from
chhurpi , a fermented milk product of Sikkim Himalayan region, resulted
in the production of a bioactive protein hydrolysate exhibiting anti-oxidant properties ( Rai et al., 2016 ). Among 125 proteolytic yeasts
isolated from chhurpi ,K. marxianus YMP45 and S. cerevisiae YAM14
fermentation resulted in a product with higher antioxidant activity ( Rai
et al., 2016).
Presence of angiotensin I-converting enzyme (ACE) inhibitory pep-
tides in fermented foods provides antihypertensive property to the
product ( Rai et al., 2017). Yeasts isolated from several fermented milk
products have shown their ability in the production of ACE inhibitorypeptides upon hydrolysis of milk proteins ( Chaves-Lopez et al., 2012;
García-Tejedor et al., 2014). Among 89 yeast isolates, P. kudriavzevii
KL84A and K. marxianus KL26A isolated from kumis (Colombian tra-
ditional fermented milk product) have shown their ability to produceACE inhibitory peptides ( Chaves-Lopez et al., 2012 ). Further, it was
shown that milk fermented with single cultures of Galactomyces geo-
trichum KL20B and K. marxianus KL26A resulted in higher ACE in-
hibitory peptides in comparison to mixed culture fermentation alongwith LAB ( Chaves-Lopez et al., 2012 ). Earlier, Li et al. (2015) have
identified novel peptides (VLSRYP and LRFF) exhibiting ACE inhibitory
activity from fermented milk using K.
marxianus and optimized the
fermentation conditions using response surface methodology.
Yeast species belonging Debaryomyces hansenii ,K. lactis and K.
marxianus were assessed for the production of protein hydrolysate
having antihypertensive e ffect and reported to exhibit both invitro and
invivo antihypertensive properties ( Garcia-Tejedor, Padilla, Salom,
Belloch, & Manzanares, 2013). Casein hydrolysates prepared using D.
hansenii strains also exhibited ACE inhibitory activity, which was due to
the production of the bioactive peptides, LHLPLP and HLPLP ( García-
Tejedor, Sánchez-Rivera, Recio, Salom, & Manzanares, 2015 ). Novel
ACE inhibitory peptides (DPYKLRP, YKLRP, PYKLRP and GILRP) were
released from bovine lactoferrin hydrolysed by K. marxianus which also
showed antihypertensive e ffect in spontaneously hypertensive rats
(García-Tejedor et al., 2014 ). Production of bioactive peptides using
yeast from di fferent fermented foods needs to be explored further as
yeast proteases can result in the release of several novel biologically
active peptides having speci fic health bene fits.6. Production of organically bound selenium yeast
Selenium (Se) is an essential micronutrient, which is important due
to its role in prevention of cancer and anti-ageing properties ( Abedi
et al., 2018). Yeast cells can be used for the production of functional
foods enriched with Se as they have the ability to accumulate and
transform inorganic Se to its organic form ( Sanchez-Martrinez et al.,
2012 ;Wang, Yang, Wei, Liu, & Wang, 2012). Transformation of selenite
was carried out during white wine fermentation using S. cerevisiae and
Saccharomyces bayanus , and selenomethionine was found to be the main
Se-compound in the final product ( Perez-Corona et al., 2011 ). Se-en-
riched beer having selenomethionine as the main compound was pro-duced by fermentation using S. cerevisiae and Saccharomyces uvarum
(Sanchez-Martrinez et al., 2012). Se-enriched S. cerevisiae administra-
tion to rats reduced colorectal cancer progression by di fferent me-
chanisms including altering the function of BCL2, p53 and CD3 andreduction in the size and number of aberrant crypt foci ( Abedi et al.,
2018 ). Supplementation of Se enriched yeast reduced the growth of
brain metastatic tumor suggesting its application in prevention of brain
metastatic disease ( Wrobel, Seelbach, Chen, Power, & Toborek, 2013).
Apart from Saccharomyces , yeasts belonging to the genus Candida have
also been shown to have the ability to bind with Se ( Wang et al., 2012).
Se-enriched C.
utilis was prepared by addition of sodium selenite and its
effect on antioxidant capacity of rats was studied ( Yang, Wang, Wei,
Liu, & Ge, 2013 ). It was found that optimum dietary supplement of Se-
enriched C. utilis enhanced antioxidant capacity in rats. Selenized C.
utilis has been also shown to improve immunity factors and antioxidant
capacity apart from improved growth performance compared to the
control group, in rats ( Wang et al., 2012).
7. Impact of yeast on functional properties during mixed culturefermentation
Yeast can have an impact on the functional foods industry as it plays
a major role during food fermentation and development of bioprocessesfor production of nutraceuticals. Additionally, yeasts play a bene ficial
role during food fermentation by supporting the key microorganismresponsible for product development ( Rai & Jeyaram, 2017). Further,
yeasts are also responsible for reduction or elimination of undesirablespoilage causing microorganisms that are responsible for poor product
quality by the production of mycotoxin, organic acids and antibiotic
factors ( Rai & Jeyaram, 2017). Interaction of yeasts with lactic acid
bacteria (LAB) and filamentous fungi for the improvement of functional
properties is presented in Table 2 and discussed in detail in the fol-
lowing section.
7.1. Yeast's association with bacteria in functional food production
In most of the foods fermented using LAB, the role of yeasts has been
mainly focused on changes in pH, texture, color, flavour, shelf life,
nutritional and antinutritional factors ( Rai & Jeyaram, 2017 ;Rai &
Appaiah, 2014 ). In the past two decades, yeasts have also shown to be
important for enhancement of bioactive compounds responsible for
specific health bene fits (Nakamura et al., 1995; Rai et al., 2016; Chaves-
Lopez et al., 2014). Some of the functional milk products commercia-lized for antihypertensive properties have yeast as a co-starter and milk
fermentation using combination of yeast and LAB has resulted in the
production of ACE inhibitory peptides ( Nakamura et al., 1995; Rai
et al., 2017 ). A popular fermented milk product, sour milk, having
antihypertensive e ffect in spontaneously hypertensive rats, is fermented
using Lactobacillus helveticus and S. cerevieseae as a co-culture
(Nakamura et al., 1995 ). The peptides responsible for the anti-
hypertensive e ffect were identi fied as VPP and IPP ( Nakamura et al.,
1995 ).
ACE inbibitory activity also depends on the combination of yeast
and LAB used for fermentation ( Chaves-Lopez et al., 2014). MilkA.K. Rai et al. Trends in Food Science & Technology 83 (2019) 129–137
133

fermentation carried out using a proteolytic strain of Pichia kudriavzevii
KL84A along with LAB resulted in the production of ACE inhibitory
peptides ( Chaves-Lopez et al., 2014 ). Recently, a non dairy beverage,
which is a blend of cassava and rice, fermented using mixed culturecontaining T. delbrueckii CCMA 0235 with L. plantarum CCMA 0743
resulted in a product with superior antioxidant activity in comparisonto other formulations ( Freire, Ramos, Souza, Cardoso, & Schwan,
2017 ). Proper combination of yeast and LAB has to be applied in other
fermented foods for the release of novel bioactive peptides. Yeast has
also been applied for getting better viability of probiotics by co-cul-
turing with probiotic LAB ( Liu & Tsao, 2009 ). The survival rate of Lb.
bulgaricus in yoghurt was signi ficantly improved by 10
2and 105times
after co-cultivation with yeasts, Yarrowia lipolytica B9014 and Sac-
charomyces bayanus CVC-NF74, respectively ( Liu & Tsao, 2009). Fur-
ther, yeast such as Geotrichum candidum CMICC335426 and Williopsis
saturnus CBS254 enhanced the survival rate of probiotic LAB, L. rham-
nosus DR20 by 106times during milk fermentation carried out at 30 °C
(Liu & Tsao, 2009 ). Kombucha beverage prepared using mixed culture
fermentation using Zygosaccharomyces sp. and Acetobacter sp. resulted
in higher radical scavenging activity in comparison to other yeast-bacteria combinations ( Malbasa, Lon čar, & Vitas, 2010 ). It is evident
that the proper combination of bacteria and yeast is important toachieve higher functional properties in the product.
7.2. Yeast's association with filamentous fungi in functional food production
Interaction between filamentous fungi and yeast has a positive im-
pact on several fermented products and industrially important biopro-
cesses for the production of nutraceuticals ( Feng, Passoth, Eklund-
Jonsson, Alminger, & Schnurer, 2007 ). Traditional starter cultures rich
infilamentous fungi and yeasts are used in many Asian countries for the
production of rice based fermented alcoholic beverage ( Dung et al.,
2006 ;Ghosh et al., 2015 ).Haria , a rice based beverage fermented using
a starter rich in filamentous fungi and yeast, was found to exhibit high
free radical scavenging activity and presence of malto-oligosaccharides,
which are known for their prebiotic e ffects ( Ghosh et al., 2015 ). Solid
state fermentation of okara using co-culture of Rhizopus oligosporus and
Yarrowia lipolytica resulted in higher antioxidant activity, free phe-
nolics, and free amino acids in comparison to okara fermented with
only R. oligosporus (Vong, Hua, & Liu, 2018 ).
Co-cultivation of R. oligosporus along with di fferent yeast species ( S.
boulardii ,S. cerevisiae ,K. lactis andPichia anomala ) during fermentation
of barley tempeh resulted in increase of ergosterol levels by 12 –31%
(Feng et al., 2007 ). They also observed increase in vitamins B
6and B 3in
barley tempeh prepared using co-cultivation of S. cerevisiae J191 and R.oligosporus . Yeasts have become an important part of sequential fer-
mentation processes along with filamentous fungi for production of
highly pure oligosaccharides having prebiotic properties ( Aburto,
Guerrero, Vera, Wilson, & Illanes, 2016 ;Guerrero et al., 2014; Nobre,
Goncalves, Teixeira, & Rodrigues, 2018 ;Sheu, Chang, Wang, Wu, &
Huang, 2013). Production of galacto-oligosaccharides by simultaneoussynthesis and puri fication strategy was carried out using Aspergillus
oryzae and S. cerevisiae (Aburto et al., 2016). High-purity fructooligo-
saccharides were produced by a process involving immobilized cells of
Aspergillus japonicus andPichia heimii (Sheu et al., 2013). Similarly, a co-
culture fermentation using Aspergillus ibericus andS. cerevisiae YIL162 W
was carried out for the production of fructooligosaccharides with high
purity (97.4%) ( Nobre et al., 2018). Combination of yeasts with fila-
mentous fungi is a promising approach and can be explored further forproduction of functional foods.
8. Genetic engineering of yeast for development of functional food
and additives
A genetic engineering approach has been used for improving the
efficiency of yeast strains for the production of speci fic enzymes useful
for making high value functional food additives. Production of selected
high value nutraceuticals by modi fied host yeast cells is presented in
Table 3 . Fructo-oligosaccharides are chains of the fructose molecule
that exhibit prebiotic properties and they are gaining attention as an
important functional food ingredient. In a recent study, Yarrowia lipo-
lytica strain Enop56 in which endoilunase gene was over expressed
resulted in the higher yield of fructo-oligosaccharides from inulin ( Han
et al., 2017). High yield of fructo-oligosaccharides was obtained from aone-step bioprocess using recombinant yeast S. cerevisiae JZH expressed
with heterologous endo-inulinase gene ( Wang et al., 2016). Bioengi-
neering of wine yeast has also been carried out to elevate folate content
in wine by overexpressing folate biosynthesis gene FOL2 ( Walkey et al.,
2015 ). Recently, S. cerevisiae was engineered for the production of 6 six
flavanoids (quercetin, liquiritigenin, naringenin, resokaempferol,
kaempferol and fisetin) from glucose ( Rodriguez et al., 2017 ). Nar-
ingenin, a flavonoid was produced by an engineered S. cerevisiae by co-
expression
of speci fic naringenin production genes from Arabidopsis
thaliana (Koopman et al., 2012 ). Selenium-methylselenocysteine, one of
the important selenium metabolites that is present in selenium-enriched
diets and shows a bene ficial effect in prevention of cancer, was pro-
duced by an engineered S. cerevisiae strain ( Mapelli, Hillestrøm,
Kapolna, Larsen, & Olsson, 2011 ).
Metabolic engineering has also been used for the production of
carotenoids by di fferent yeast cells, which do not possess anyTable 2
Association of yeasts with lactic acid bacteria and filamentous fungi for enhancement of functional properties.
Product Yeast species Partner organisms Functional properties References
Yeast association with lactic acid bacteria (LAB)
Sour milk Saccharomyces cerevisiae Lactobacillus helviticus Antihypertensive properties Nakamura, Yamamoto, Sakai, and
Takano (1995)
Fermented milk S. cerevisiae K7 Lactococcus lactis NBRC 12007 ACE- inhibitory properties Rasika et al. (2015)
Cassava and rice based
beverageTorulaspora delbrueckii CCMA
0235L. plantarum CCMA 0743 Antioxidant activity Freire et al. (2017)
Fermented milk Pichia kudriavzevii KL84A Lactobacillus plantarum LAT3,
Enterococcus faecalis KL06ACE- inhibitory properties Chaves-Lopez et al. (2014)
Fermented soya milk Saccharomyces boulardii LAB Increase in aglycones iso flavones
and antioxidant activityRekha and Vijayalakshmi (2008)
Fermented milk S. boulardii LAB Antioxidant activity Parrella et al. (2012)
Idli batter Saccharomyces boulardii SAA655 Lactococcus lactis N8 Increased ribo flavin and folate
levelsRajendran, Chamlagain, Kariluoto,
Piironen, and Saris (2017)
Kombucha beverage Zygosaccharomyces sp. Acetobacter sp. Antioxidant properties Malbasa et al., 2010
Yeast association with filamentous fungi
Okara fermentation Yarrowia lipolytica Rhizopus oligosporus antioxidant activity Vong et al. (2018)
Barley tempeh S. boulardii J551 R. oligosporus J401 Increased ergosterol Feng et al. (2007)
S. cerevisiae J191 R. oligosporus J401 Increased niacinamideA.K. Rai et al. Trends in Food Science & Technology 83 (2019) 129–137
134

components of the carotenoid biosynthesis pathway ( Misawa &
Shimada, 1997). Among several yeasts, S. cerevisiae have been ideal and
are the most commonly used host strain for the production of car-
otenoids by metabolic engineering ( Chen et al., 2016; Xie, Lv, Ye, Zhou,
& Yu, 2015 ;Zhou, Ye, Xie, Lv, & Yu, 2015 ). Lycopene, a carotenoid
nutraceutical possessing antioxidant and anti-cancer properties was
overproduced in S. cerevisiae by combining host engineering and
pathway engineering ( Chen et al., 2016 ). Recently, host and pathway
engineering strategy was adopted for enhanced production of lycopene
using engineered Y. lipolytica strain ( Schwartz, Frogue, Misa, &
Wheeldon, 2017). Metabolic engineering has also been applied for theproduction of lycopene by Pichia pastoris X-33 ( Bhataya et al., 2009 ).
The strain optimized for the production of lycopene overexpressed 8genes including single copies of EGR8, MVD1, CrtE and CrtB, and two
copies of CrtI and HMG1. S. cerevisiae has been e fficiently engineered
for the production of astaxanthin, a high value carotenoid with strongantioxidant activity, resulting in an appreciable astaxanthin production
of 4.7 mg/g ( Zhou et al., 2015). Production of resveratrol, an anti-
oxidant from natural resources, is expensive due to limited availabilityof resveratrol rich plants. Production of resveratrol (titre value –
800 mg/L) was achieved by fed batch fermentation technique using agenetically engineered S. cerevisiae (Li, Schneider, Kristensen, Borodina,
& Nielsen, 2016 ).
Yeasts can also produce polyunsaturated fatty acids (PUFA), in-
cluding linolenic acid, eicosapentaenoic acid (EPA) and docosahex-
aenoic acid (DHA), that are known to exhibit several health bene fits
and are consequently an important nutraceutical for the functional foodindustry. In recent years, the genetic engineering approach has been
applied for the production of PUFA using host yeast cells ( Sun et al.,
2017 ;Uemura, 2012; Xue et al., 2013 ). EPA production yielding 15%
by dry cell weight was obtained by the metabolic engineering of Y.
lipolytica strain ( Xue et al., 2013 ). It was achieved by balancing the
expression of EPA biosynthetic pathway genes and modifying the host
metabolism. Production of linolenic acid by genetically engineering
yeast strains has also been reported in S. cerevisiae (Uemura, 2012 ),Y.
lipolytica (Sun et al., 2017 ) and Trichosporon oleagenosus ATCC20509
(Gorner et al., 2016 ). In the future, the genetic engineering approach is
expected to have more application in the creation of viable bioprocessesfor production of nutraceuticals using di fferent types of yeasts.9. Conclusions
Based on traditional knowledge as well as recent scienti fic evi-
dences,
yeasts are one of the important players in food biotechnology
for the development of functional foods and nutraceuticals. Yeasts haveshown their application in the production of bioactive metabolites and
development of bioprocesses for substrate derived nutraceutical pro-
duction. Several bioprocesses have been developed which involve yeast
as a single starter or as a mixed starter along with LAB and filamentous
fungi for the production of many industrially important nutraceuticals.Due to increase in awareness of the role of yeast on production of nu-
traceuticals, selection of potential yeast strains for improvement of
functional properties of the product has become an important criterion.
Modern biotechnological tools have also been applied resulting in the
development of recombinant yeasts with improved features for the
production of nutraceuticals. However, yeasts from many unexplored
traditional fermented foods remain unexploited for technological
properties for the development of functional foods and nutraceuticals.
Conflicts of interest
The authors declare “no con flict of interest. ”
Acknowledgements
The authors of the manuscript thank Institute of Bioresources and
Sustainable Development (IBSD), an Autonomous Institute of
Department of Biotechnology, Govt. of India for all the support, en-
couragement and providing necessary funding and help to undertake
the study. We thank Dr. Sangeetha Ravi Kumar, Moran Eye Center,
University of Utah, Utah for correcting the grammatical errors in the
manuscript.
References
Abedi, J., Saatloo, M. V., Nejati, V., Hobbenaghi, R., Tukmechi, A., et al. (2018).
Selenium-enriched saccharomyces cerevisiae reduces the progression of colorectal
cancer. Biological Trace Elemental Research, 185 , 424 –432.
Aburto, C., Guerrero, C., Vera, C., Wilson, L., & Illanes, A. (2016). Simultaneous synthesis
and puri fication (SSP) of galactooligosaccharides in batch operation. Lebensmittel-
Wissenschaft und -Technologie- Food Science and Technology, 72 ,8 1 –89.
Al-Manhel, A. J., & Niamah, A. K. (2017). Mannan extract from Saccharomyces cerevisiae
used as prebiotic in bioyogurt production from bu ffalo milk. International FoodTable 3
Genetic engineering of yeasts for the production of nutraceuticals.
Nutraceuticals Yeast species Improvement References
Fructooligosaccharides Saccharomyces cerevisiae JZH Yeast expressed with endo-inulinase gene Wang et al. (2016)
Fructooligosaccharides Yarrowia lipolytica strain
Enop56Endo-inulinase gene from Aspergillus niger was overexpressed Han et al. (2017)
Six Flavanoids S. cerevisiae Reconstruction of long biosynthetic pathways having eight
heterologous genesRodriguez et al. (2017)
Naringenin S. cerevisiae Coexpressing the naringenin production genes from Arabidopsis
thalianaKoopman et al. (2012)
Resveratrol, naringenin, genistein,
kaempferol and quercetinS. cerevisiae Yeast strains engineered harboring plasmids with heterologous
genes for enzymes responsible for biosynthesisTrantas, Panopoulos, &Ververidis, 2009
Resveratrol S. cerevisiae strains Reconstruction of resveratrol biosynthetic pathway in S. cerevisiae Li et al. (2016)
Lycopene Pichia pastoris X-33 heterologous expression of lycopene-pathway enzymes Bhataya et al., 2009
Lycopene S. cerevisiae CEN.PK2 Over expression of lycopene by engineering both host cell and
heterologous pathwayChen et al. (2016)
Kaempferol S. cerevisiae Construction of biosynthesis pathway of kaempferol Duan et al. (2017)
Astaxanthin S. cerevisiae Introduction of codon-optimized Haematococcuspluvialis crtZ and
bktZhou et al. (2015)
Lycopene Y. lipolytica Codon-optimized genes crtBandcrtIofPantoea ananatis were
expressedMatthaus, Ketelhot, Gatter,and Barth (2014)
Lycopene S. cerevisiae Combining directed evolution and metabolic engineering Xie et al. (2015)
Lycopene Y. lipolytica Mevalonate pathway overexpression Schwartz et al. (2017)
γ-linolenic acid Y. lipolytica Introduction of codon-optimized △6-desaturase from Mortierella
alpinaSun et al. (2017)
Eicosapentaenoic acid Y. lipolytica Expression of pathway genes for EPA production Xue et al. (2013)A.K. Rai et al.
Trends in Food Science & Technology 83 (2019) 129–137
135

Research Journal, 24 , 2259 –2264 .
Aloglu, H. S., Ozer, E. G., & Oner, Z. (2016). Assimilation of cholesterol and probiotic
characterization of yeast strains isolated from raw milk and fermented foods.
International Journal of Dairy Technology, 69 ,6 3 –70.
Amorim, J. C., Piccoli, R. H., & Duarte, W. F. (2018). Probiotic potential of yeasts isolated
from pineapple and their use in the elaboration of potentially functional fermented
beverages. Food Research International, 107 , 518 –527.
Bhataya, A., Schmidt-Dannert, C., & Lee, P. C. (2009). Metabolic engineering of Pichia
pastoris X-33 for lycopene production. Process Biochemistry, 44 , 1095 –1102 .
Borchani, C., Fonteyn, F., Jamin, G., Paquot, M., Thonart, P., & Blecker, C. (2016).
Physical, functional and structural characterization of the cell wall fractions frombaker's yeast Saccharomyces cerevisiae .Food Chemistry, 194 , 1149 –1155 .
Chaves-Lopez, C., Serio, A., Paparella, A., Martuscelli, M., Corsetti, A., Tofalo, R., et al.
(2014). Impact of microbial cultures on proteolysis and release of bioactive peptidesin fermented milk. Food Microbiology, 42 , 117 –121.
Chaves-Lopez, C., Tofalo, R., Serio, A., Paparella, A., Sacchetti, G., & Suzzi, G. (2012).
Yeasts from Colombian Kumis as source of peptides with Angiotensin I converting
enzyme (ACE) inhibitory activity in milk. International Journal of Food Microbiology,
159,3 9 –46.
Chen, Y., Xiao, W. H., Wang, Y., Liu, H., Li, X., & Yuan, Y. J. (2016). Lycopene over-
production in Saccharomyces cerevisiae through combining pathway engineering with
host engineering. Microbial Cell Factories .https://doi.org/10.1186/s12934-016-
0509-4 .
Chua, J. Y., Lu, Y., & Liu, S. Q. (2017). Biotransformation of soy whey into soy alcoholic
beverage by four commercial strains of Saccharomyces cerevisiae .International Journal
of Food Microbiology, 262 ,1 4 –22.
De Araujo, T. V., Andrade, E. F., Lobato, R. V., Orlando, D. R., Gomes, N. F., de Sousa, R.
V., et al. (2016). E ffects of beta-glucans ingestion ( Saccharomyces cerevisiae ) on me-
tabolism of rats receiving high-fat diet. Journal of Animal Physiology and Animal
Nutrition, 101 , 349 –358.
Dinleyici, E. C., Kara, A., Ozen, M., & Vandenplas, Y. (2014). Saccharomyces boulardii
CNCM I-745 in di fferent clinical conditions. Expert Opinion on Biological Therapy, 14 ,
1593 –1609 .
Duan,
L., Ding, W., Liu, X., Cheng, X., Cai, J., Hua, E., et al. (2017). Biosynthesis and
engineering of kaempferol in Saccharomyces cerevisiae .Microbial Cell Factories, 16 ,
165.
Dung, N. T. P., Rombouts, F. M., & Nout, M. J. R. (2006). Functionality of selected strains
of moulds and yeasts from Vietnamese rice wine starters. Food Microbiology, 23 ,
331 –340.
EFSA (2011). Scienti fic opinion on the safety of ‘yeast beta-glucans ’as a novel food in-
gredient. EFSA Journal, 9 (5), 2137 –2159 .
Fadda, M. E., Mossa, V., Deplano, M., Pisano, M. B., & Cosentino, S. (2017). In vitro
screening of Kluyveromyces strains isolated from Fiore Sardo cheese for potential use
as probiotics. LWT -Food Science and Technology, 75 , 100 –106.
Fai, A. E. C., Simiqueli, A. P. R., Ghiselli, G., & Pastore, G. M. (2015). Sequential opti-
mization approach for prebiotic galactooligosaccharides synthesis by Pseudozyma
tsukubaensis and Pichia kluyveri .LWT -Food Science and Technology, 63 , 1214 –1219 .
Feng, X. M., Passoth, V., Eklund-Jonsson, C., Alminger, M. L., & Schnurer, J. (2007).
Rhizopus oligosporus and yeast co-cultivation during barley tempeh fermentation –nu-
tritional impact and real-time PCR quanti fication of fungal growth dynamics. Food
Microbiology, 24 , 393 –402.
Fernández-Arrojo, L., Marín, D., Gómez De Segura, A., Linde, D., Alcalde, M., Gutiérrez-
Alonso, P., et al. (2007). Transformation of maltose into prebiotic iso-maltooligosaccharides by a novel a-glucosidase from Xantophyllomyces dendrorhous .
Process Biochemistry, 42 , 1530 –1536 .
Freire, A. L., Ramos, C. L., Souza, P. N. C., Cardoso, M. G. B., & Schwan, R. F. (2017).
Nondairy beverage produced by controlled fermentation with potential probioticstarter cultures of lactic acid bacteria and yeast. International Journal of Food
Microbiology, 248 ,3 9 –46.
Gaensly, F., Agustini, B. C., Silva, G. A. D., & Picheth, G. T. M. B. (2015). Bon fim,
Autochthonous yeasts with β-glucosidase activity increase resveratrol concentration
during the alcoholic fermentation of Vitis labrusca grape must. Journal of Functional
Foods, 19 , 288 –295.
Galinari, E., Almeida-Lima, J., Macedo, G. R., Mantovani, H. C., & Rocha, H. A. O. (2018).
Antioxidant,
antiproliferative, and immunostimulatory e ffects of cell wall -d-mannan
fractions from Kluyveromyces marxianus .International Journal of Biological
Macromolecules, 109 , 837 –846.
Galinari, E., Sabry, D. A., Sassaki, G. L., Macedo, G. R., Passos, F. M., Mantovani, H. C.,
et al. (2017). Chemical structure, antiproliferative and antioxidant activities of a cellwall a-d-mannan from yeast. Kluyveromyces marxianus. Carbohydrate Polymers, 157 ,
1298 –1305 .
Garcia-Tejedor, A., Padilla, B., Salom, J. B., Belloch, C., & Manzanares, P. (2013). Dairy
yeasts produce milk protein derived antihypertensive hydrolysates. Food Research
International, 53 , 203 –208.
García-Tejedor, A., Sánchez-Rivera, L., Castelló-Ruiz, M., Recio, I., Salom, J. B., &
Manzanares, P. (2014). Novel antihypertensive lactoferrin-derived peptides producedbyKluyveromyces marxianus : Gastrointestinal stability profi le and in vivo angiotensin
I-converting enzyme (ACE) inhibition. Journal of Agricultural and Food Chemistry, 62 ,
1609 –1616 .
García-Tejedor, A., Sánchez-Rivera, L., Recio, I., Salom, J. B., & Manzanares, P. (2015).
Dairy Debaryomyces hansenii strains produce the antihypertensive casein derived
peptides LHLPLP and HLPLP. LWT –Food Science and Technology, 61 , 550 –556.
Ghosh, K., Ray, M., Adak, A., Dey, P., Halder, S. K., Das, A., et al. (2015). Microbial,
saccharifying and antioxidant properties of an Indian rice based fermented beverage.Food Chemistry, 168 , 196 –202.
Gorner, C., Redai, V., Bracharz, F., Schrepfer, P., Garbe, D., & Brück, T. (2016). Geneticengineering and production of modi fied fatty acids by the non-conventional oleagi-
nous yeast Trichosporon oleaginosus ATCC 20509. Green Chemistry, 18 , 2037 –2046 .
Greppi, A., Saubade, F., Botta, C., Humblot, C., Guyot, J. P., & Cocolin, L. (2017).
Potential probiotic Pichia kudriavzevii strains and their ability to enhance folate
content of traditional cereal-based African fermented food. Food Microbiology, 62 ,
169 –177.
Guerrero, C., Vera, C., Novoa, C., Dumont, J., Acevedo, F., & Illanes, A. (2014).
Purifi cation of highly concentrated galacto-oligosaccharide preparations by selective
fermentation with yeasts. International Dairy Journal, 39 ,7 8 –88.
Han, S. M., Jeon, S. J., Lee, H. B., & Lee, J. S. (2016). Screening of γ-aminobutyric acid
(GABA)-producing wild yeasts and their microbiological characteristics. Korean
Journal of Mycology, 44 ,8 7 –93.
Han,
S. M., & Lee, J. S. (2017). Production and its anti-hyperglycemic e ffects of γ-ami-
nobutyric acid from the wild yeast strain Pichia silvicola UL6-1 and Sporobolomyces
carnicolor 402-JB-1. Mycobiology, 45 , 199 –203.
Han, Y. Z., Zhou, C. C., Xu, Y. Y., Yao, J. X., Chi, Z., Chi, Z. M., et al. (2017). High-e fficient
production of fructo-oligosaccharides from inulin by a two-stage bioprocess using an
engineered Yarrowia lipolytica strain. Carbohydrate Polymers, 173 , 592 –599.
Heinonen, M., Lehtonen, P. J., & Hopla, A. (1998). Antioxidant activity of berry and fruit
wines and liquor. Journal of Agricultural and Food Chemistry, 48 ,2 5 –31.
Hjortmo, S. B., Hellstrom, A. M., & Andlid, T. A. (2008a). Production of folates by yeasts
in Tanzanian fermented togwa. FEMS Yeast Research, 8 , 781 –787.
Hjortmo, S., Patring, J., Jastrebova, J., & Andlid, T. (2008b). Bioforti fication of folates in
white wheat bread by selection of yeast strain and process. International Journal of
Food Microbiology, 127 ,3 2 –36.
Ilowefah, M., Bakar, J., Ghazali, H. M., Mediani, A., & Muhammad, K. (2014).
Physicochemical and functional properties of yeast fermented brown rice flour.
Journal of Food Science & Technology, 52 , 5534 –5545 .
Jaehrig, S. C., Rohn, S., Kroh, L. W., Fleischer, L. G., & Kurz, T. (2007). In Vitro potential
antioxidant activity of (1/3), (1/6)-b-D-glucan and protein fractions from
Saccharomyces cerevisiae cell walls. Journal of Agricultural and Food Chemistry, 55 ,
4710 –4716 .
Jaehrig, S. C., Rohn, S., Kroh, L. W., Wildenauer, F. X., Lisdat, F., Fleischer, L., et al.
(2008). Antioxidative activity of (1 →3), (1→6)–d-glucan from Saccharomyces cere-
visiae grown on di fferent media. Lebensmittel-Wissenschaft und -Technologie: Food
Science and Technology, 41 , 868 –877.
Javmen, A., Nemeikait ė-Čėnien ė, A., Bratchikov, M., Grigi škis, S., Grigas, F., Jonauskien ė,
I., et al. (2015). β-glucan from Saccharomyces cerevisiae induces IFN-gamma pro-
duction in vivo in BALB/c mice. In Vivo, 29 , 359 –363.
Kariluoto, S., Aittamaa, M., Korhola, M., Salovaara, H., Vahteristo, L., & Piironen, V.
(2006). E ffects of yeasts and bacteria on the levels of folates in rye sourdoughs.
International Journal of Food Microbiology, 106 , 137 –143.
Kelesidis, T., & Pothoulakis, C. (2012). E fficacy and safety of the probiotic Saccharomyces
boulardii for the prevention and therapy of gastrointestinal disorders. Therapeutics
Advances in Gastroenterology, 5 , 111 –125.
Koopman, F., Beekwilder, J., Crimi, B., van Houwelingen, A., Hall, R. D., Bosch, D., et al.
(2012). De novo production of the flavonoid naringenin in engineered Saccharomyces
cerevisiae .Microbial Cell Factories, 11 , 155 .
Korhola, M., Hakonen, R., Juuti, K., Edelmann, M., Kariluoto, S., & Piironen, V. (2014).
Production of folate in oat bran fermentation by yeasts isolated from barley and di-verse foods. Journal of Applied Microbiology, 117 , 679 –689.
Kumura, H., Tanoue, Y., Tsukahara, M., Tanaka, T., & Shimazaki, K. (2004). Screening of
dairy yeast strains for probiotic applications. Journal of Dairy Science, 87 , 4050 –4056 .
Kwiatkowski, S. (2009). A study of Saccharomyces cerevisiae cell wall glucans. Journal of
the Institute of Brewing, 115 , 151 –158.
Liang, G. B., Du, G. C., & Chen, J. (2009). Salt-induced osmotic stress for glutathione
overproduction in Candida utilis. Enzyme and Microbial Technology, 45 , 324 –329.
Li, Y., Sadiq, F. A., Liu, T. J., Chen, J. C., & He, G. Q. (2015). Puri fication and identi fi-
cation of novel peptides with inhibitory e ffect against angiotensin I-converting en-
zyme and optimization of process conditions in milk fermented with the yeastKluyveromyces marxianus .Journal of Functional Foods, 16 , 278 –288.
Li, M., Schneider, K., Kristensen, M., Borodina, I., & Nielsen, J. (2016). Engineering yeast
for high-level production of stilbenoid antioxidants. Scientific Reports, 6 , 36827.
https://doi.org/10.1038/srep36827 .
Liu,
S. Q., & Tsao, M. (2009). Enhancement of survival of probiotic and non-probiotic
lactic acid bacteria by yeasts in fermented milk under non-refrigerated conditions.
International Journal of Food Microbiology, 135 ,3 4 –38.
Malbasa, R. V., Lon čar, E. S., & Vitas, J. S. (2010). Čanadanovi ć-Brunet JM. In fluence of
starter cultures on the antioxidant activity of kombucha beverage. Food Chemistry,
127, 1727 –1731 .
Mannazzu, I. S., Landolfo, T. L., & Buzzini, P. (2015). Red yeasts and carotenoid pro-
duction: Outlining a future for non-conventional yeasts of biotechnological interest.
World Journal of Microbiology and Biotechnology, 31 , 1665 –1673 .
Mapelli, V., Hillestrøm, P. R., Kapolna, E., Larsen, E. H., & Olsson, L. (2011). Metabolic
and bioprocess engineering for production of selenized yeast with increased content
of seleno-methylselenocysteine. Metabolic Engineering, 13 , 282 –293.
Matthaus, F., Ketelhot, M., Gatter, M., & Barth, G. (2014). Production of lycopene in the
noncarotenoid-producing yeast Yarrowia lipolytica .Applied and Environmental
Microbiology, 80 , 1660 –1669 .
Maugeri, F., & Hernalsteens, S. (2007). Screening of yeast strains for transfructosylating
activity. Journal of Molecular Catalysis B: Enzymatic, 49 ,4 3 –49.
Misawa, N., & Shimada, H. (1997). Metabolic engineering for the production of car-
otenoids in non-carotenogenic bacteria and yeasts. Journal of Biotechnology, 59 ,
169 –181.
Moline, M., Libkind, D., & Van Broock, M. (2012). Production of torularhodin, torulene,
andβ-carotene by Rhodotorula yeasts .Methods in Molecular Biology, 898 , 275 –283.A.K. Rai et al. Trends in Food Science & Technology 83 (2019) 129–137
136

Musatti, A., Manzoni, M., & Rollini, M. (2013). Postfermentative production of glu-
tathione by baker's yeast ( S. cerevisiae ) in compressed and dried forms. New Biotech,
30, 219 –226.
Nakamura, Y., Yamamoto, N., Sakai, K., & Takano, T. (1995). Antihypertensive e ffect of
sour milk and peptides isolated from it that are inhibitors to angiotensin I converting
enzyme. Journal of Dairy Science, 78 , 1253 –1257 .
Nobre, C., Castro, C. C., Hantson, A.-L., Teixeira, J. A., De Weireld, G., & Rodrigues, L. R.
(2016). Strategies for the production of high-content fructo-oligosaccharides throughthe removal of small saccharides by co-culture or successive fermentation with yeast.
Carbohydrate Polymers, 136 , 274 –281.
Nobre, C., Goncalves, D. A., Teixeira, J. A., & Rodrigues, L. R. (2018). One-step co-culture
fermentation stratagy to produce high content fructo-oligosaccharides. Carbohydrate
Polymers, 201 ,3 1 –38.
Ogunremi, O. R., Sanni, A. I., & Agrawal, R. (2015). Hypolipidaemic and antioxidant
effects of functional cereal-mix produced with probiotic yeast in rats fed high cho-
lesterol diet. Journal of Functional Foods, 17 , 742 –748.
Padilla, B., Frau, F., Ruiz-Matute, A. I., Montilla, A., Belloch, C., Manzanares, P., et al.
(2015). Production of lactulose oligosaccharides by isomerisation of transgalactosy-lated cheese whey permeate obtained by β-galactosidases from dairy Kluyveromyces.
Journal of Dairy Research, 82 , 356 –364.
Parrella, A., Caterino, E., Cangiano, M., Criscuolo, E., Russo, C., Lavorgna, M., et al.
(2012). Antioxidant properties of di fferent milk fermented with lactic acid bacteria
and yeast. International Journal of Food Science and Technology, 47 , 2493 –2502 .
Patring, J. D. M., Hjortmo, S. B., Jastrebova, J. A., Svensson, U. K., Andlid, T. A., &
Jägerstad, I. M. (2006). Characterization and quanti fication of folates produced by
yeast strains isolated from ke fir granules. European Food Research and Technology,
223, 633 –637.
Pelizon, A. C., Kaneno, R., Soares, A. M. V., Meira, D. A., & Sartori, A. (2005).
Immunomodulatory activities associated with b-Glucan derived from Saccharomyces
cerevisiae .Physiological Research, 54 , 557 –564.
Perez-Corona, M. T., Sánchez-Martínez, M., Valderrama, M. J., Rodríguez, M. E., Cámara,
C., & Madrid, Y. (2011). Selenium biotransformation by Saccharomyces cerevisiae and
Saccharomyces bayanus during white wine manufacture: Laboratory-scale experi-
ments. Food Chemistry, 124 , 1050 –1055 .
Pownall, T. L., Udenigwe, C. C., & Aluko, R. E. (2010). Amino acid composition and
antioxidant
properties of pea seed (Pisum sativum L.) enzymatic protein hydrolysate
fractions. Journal of Agricultural and Food Chemistry, 58 , 4712 –4718 .
Que, F., Mao, L., & Pan, X. (2006). Antioxidant activities of five Chinese rice wines and
the involvement of phenolic compounds. Food Research International, 39 , 581 –587.
Rai, A. K., & Appaiah, K. A. (2014). Application of native yeast from Garcinia ( Garcinia
xanthochumus ) for the preparation of fermented beverage: Changes in biochemical
and antioxidant properties. Food Bioscience, 5 , 101 –107.
Rai, A. K., & Jeyaram, K. (2017). Role of yeasts in food fermentation. In T. Satyanarayana,
& G. Kunze (Eds.). Yeast diversity in human welfare. Singapore: Springer .
Rai, A. K., Kumari, R., Sanjukta, S., & Sahoo, D. (2016). Production of bioactive protein
hydrolysate using the yeasts isolated from soft chhurpi. Bioresource Technology, 219 ,
239 –245.
Rai, A. K., Sanjukta, S., & Jeyaram, K. (2017). Production of angiotensin I converting
enzyme inhibitory (ACE-I) peptides during milk fermentation and their role in re-
ducing hypertension. Critical Reviews in Food Science and Nutrition, 57 , 2789 –2800 .
Rajendran, S. C. C., Chamlagain, B., Kariluoto, S., Piironen, V., & Saris, P. E. J. (2017).
Bioforti fication of ribo flavin and folate in idli batter, based on fermented cereal and
pulse, by Lactococcus lactis N8 and Saccharomyces boulardii SAA655. Journal of Applied
Microbiology, 122 , 1663 –1671 .
Rasika, D. M. D., Ueda, T., Jayakody, L. N., Suriyagoda, L. D. B., Silva, K. F. S. T., Ando, S.,
et al. (2015). ACE-inhibitory activity of milk fermented with Saccharomyces cerevisiae
K7 and Lactococcus lactis ssp. lactis NBRC 12007. Journal of the National Science
Foundation of Sri Lanka, 43 , 141 –151.
Rekha, C. R., & Vijayalakshmi, G. (2008). Biomolecules and nutritional quality of soymilk
fermented with probiotic yeast and bacteria. Applied Biochemistry and Biotechnology,
151, 452 –463.
Rodriguez-Colinas, B., De Abreu, M. A., Fernandez-Arrojo, L., De Beer, R., Poveda, A.,
Jimenez-Barbero, J., et al. (2011). Production of galacto-oligosaccharides by the -galactosidase from Kluyveromyces lactis : Comparative analysis of permeabilized cells
versus soluble enzyme. Journal of Agricultural and Food Chemistry, 59 , 10477 –10484.
Rodriguez, A., Strucko, T., Stahlhut, S. G., Kristensen, M., Svenssen, D. K., Forster, J.,
et al. (2017). Metabolic engineering of yeast for fermentative production of favo-
noids. Bioresource Technology, 245 , 1645 –1654 .
Romanin,
D. E., Llopis, S., Genoves, S., Martorell, P., Ram on, V. D., Garrote, G. L., et al.
(2015). Probiotic yeast Kluyveromyces marxianus CIDCA 8154 shows antiin-
flammatory and anti-oxidative stress properties in vivo models. Beneficial Microbes,
1–12.
Romero, A. M., Doval, M. M., Sturla, M. A., & Judis, M. A. (2004). Antioxidant properties
of polyphenol-containing extract from soybean fermented with Saccharomycescerevisiae .European Journal of Lipid Science and Technology, 106 , 424 –431.
Saber, A., Alipour, B., Faghfoori, Z., Jam, A. M., & Khosroushahi, A. Y. (2017a). Secretion
metabolites of probiotic yeast, Pichia kudriavzevii AS-12, induces apoptosis pathways
in human colorectal cancer cell lines. Nutrition Research .https://doi.org/10.1016/j.
nutres.2017.04.001 .
Saber, A., Alipour, B., Faghfoori, Z., & Khosroushahi, A. Y. (2017b). Secretion metabolites
of dairy Kluyveromyces marxianus AS41 isolated as probiotic, induces apoptosis in
different human cancer cell lines and exhibit anti-pathogenic e ffects. Journal of
Functional Foods, 34 , 408 –421.
Saikia, D., Manhar, A. K., Deka, B., Roy, R., Gupta, K., Namsa, N. D., et al. (2017).
Hypocholesterolemic activity of indigenous probiotic isolate Saccharomyces cerevisiae
ARDMC1 in a rat model. Journal of Food and Drug Analysis, 26 , 154 –162.
Sanchez-Martr ınez, M., da Silva, E. G., Perez-Corona, T., Camara, C., Ferreira, S. L. C., &
Madrid, Y. (2012). Selenite biotransformation during brewing. Evaluation by
HPLC –ICP-MS Talanta, 88 , 272 –276.
Schwartz, C., Frogue, K., Misa, J., & Wheeldon, I. (2017). Host and pathway engineering
for enhanced lycopene biosynthesis in Yarrowia lipolytica .Frontiers in Microbiology, 8 ,
2233. https://doi.org/10.3389/fmicb.2017.02233 .
Sheu, D. C., Chang, J. Y., Wang, C. Y., Wu, C. T., & Huang, C. J. (2013). Continuous
production of high-purity fructooligosaccharides and ethanol by immobilized
Aspergillus japonicus and Pichia heimii .Bioprocess and Biosystems Engineering, 36 ,
1745 –1751 .
Song, N. E., & Baik, S. H. (2014). Identi fication and characterization of high GABA and
low biogenic amine producing indigenous yeasts isolated from Korean traditional
fermented Bokbunja ( Rubus coreanus Miquel ) wine. Journal of Biotechnology, 185S ,
S83.
Sun,
M. L., Madzak, C., Liu, H. H., Song, P., Ren, L. J., Huang, H., et al. (2017).
Engineering Yarrowia lipolytica for efficient γ-linolenic acid production. Biochemical
Engineering Journal, 117 , 172 –180.
Sun, H., You, S., Wang, M., Qi, W., Su, R., & He, Z. (2016). Recyclable strategy for the
production of high-purity galacto-oligosaccharides by Kluyveromyces lactis .Journal of
Agricultural and Food Chemistry, 59 , 10477 –10484 .
Szajewska, H., & Ko łodziej, M. (2015). Systematic review with meta-analysis:
Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea in
children and adults. Alimentary Pharmacology & Therapeutics, 42 , 1149 –1157 .
Trantas, E., Panopoulos, N., & Ververidis, F. (2009). Metabolic engineering of the com-
plete pathway leading to heterologous biosynthesis of various flavonoids and stil-
benoids in Saccharomyces cerevisiae. Metabolic Engineering, 11 , 355 –366.
Uemura, H. (2012). Synthesis and production of unsaturated and polyunsaturated fatty
acids in yeast: Current state and perspectives. Applied Microbiology and Biotechnology,
95,1–12.
Vieira, E. F., Carvalho, J., Pinto, E., Cunha, S., Almeida, A. A., & Ferreira, I. M. P. L. V. O.
(2016). Nutritive value, antioxidant activity and phenolic compounds profi le of
brewer's spent yeast extract. Journal of Food Composition and Analysis, 52 ,4 4 –51.
Vong, W. C., Au Yang, K. L. C., & Liu, S. Q. (2016). Okara (soybean residue) bio-
transformation by yeast Yarrowia lipolytica .International Journal of Food Microbiology,
235,1–9.
Vong, W. C., Hua, X.,Y., & Liu, S.-Q. (2018). Solid-state fermentation with Rhizopus oli-
gosporus andYarrowia lipolytica improved nutritional and flavour properties of okara.
Lebensmittel-Wissenschaft und -Technologie- Food Science and Technology, 90 , 316 –322.
Walkey, C. J., Kitts, D. D., Liu, Y., & Van Vuuren, H. J. J. (2015). Bioengineering yeast to
enhance folate levels in wine. Process Biochemistry, 50 , 205 –210.
Wang, D., Li, F. L., & Wang, S. A. (2016). A one-step bioprocess for production of high-
content fructo-oligosaccharides from inulin by yeast. Carbohydrate Polymers, 151 ,
1220 –1226 .
Wang,
D., Yang, B., Wei, G., Liu, Z., & Wang, C. (2012). E fficient preparation of selenium/
glutathione-enriched Candida utilis and its biological e ffects on rats. Biological Trace
Element Research, 150 , 249 –257.
Wrobel, J. K., Seelbach, M. J., Chen, L., Power, R. F., & Toborek, M. (2013).
Supplementation with selenium-enriched yeast attenuates brain metastatic growth.Nutrition and Cancer, 65 , 563 –570.
Xie, W. P., Lv, X. M., Ye, L. D., Zhou, P. P., & Yu, H. W. (2015). Construction of lycopene
overproducing Saccharomyces cerevisiae by combining directed evolution and meta-
bolic engineering. Metabolic Engineering, 30 ,6 9 –78.
Xue, Z., Sharpe, P., Hong, S. P., Yadav, N., Xie, D., Short, D., et al. (2013). Production of
omega-3 eicosapentaenoic acid by metabolic engineering of Yarrowia lipolytica .
Nature Biotechnology, 31 , 734 –740.
Yang, B., Wang, D., Wei, G., Liu, Z., & Ge, X. (2013). Selenium-enriched Candida utilis:
Efficient preparation with L-methionine and antioxidant capacity in rats. Journal of
Trace Elements in Medicine & Biology, 27 ,7–11.
Zhou, P. P., Ye, L. D., Xie, W. P., Lv, X. M., & Yu, H. W. (2015). Highly e fficient bio-
synthesis of astaxanthin in Saccharomyces cerevisiae by integration and tuning of algal
crtZ and bkt. Applied Microbiology and Biotechnology, 99 , 8419 –8428 .A.K. Rai et al.
Trends in Food Science & Technology 83 (2019) 129–137
137