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Engineering Saccharomyces cerevisiae for Production of Fatty Acids and Their Derivatives

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Genetics and Biotechnology

Part of the book series: The Mycota ((MYCOTA,volume 2))

Abstract

A sustainable production of pharmaceuticals, chemicals, and biofuels is indispensable for an environmentally friendly future. Many of these compounds are based on fatty acids and their derivatives, generically referred to as oleochemicals. As an alternative to both petrochemistry and extraction from oil plants, modern approaches focus on engineering microbes for production of oleochemicals from biomass. This review describes strategies developed in Saccharomyces cerevisiae, a eukaryotic host in which substantial advances in the production of oleochemicals have been very recently achieved through a combination of metabolic engineering and optimized fermentation regimes. The survey of the available literature shows that model-based pathway optimization holds promise to enable an economically feasible production of oleochemicals in the near future.

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Abbreviations

AcCoA:

Acetyl-CoA

AcP:

Acetyl-phosphate

ALE:

Adaptive laboratory evolution

CoA:

Coenzyme A

FA:

Fatty acid(s)

FACS:

Fluorescence-activated cell sorting

FAEE:

Fatty acid ethyl ester(s)

GAP:

Glyceraldehyde-3-phosphate

gTME:

Global transcription machinery engineering

MalCoA:

Malonyl-CoA

PPP:

Pentose phosphate pathway

SE:

Steryl ester

TAG:

Triacylglycerol

TCA:

Tricarboxylic acid

TE:

Thioesterase

X5P:

Xylulose 5-phosphate

References

  • Akhtar MK, Turner NJ, Jones PR (2013) Carboxylic acid reductase is a versatile enzyme for the conversion of fatty acids into fuels and chemical commodities. Proc Natl Acad Sci U S A 110:87–92

    CAS  PubMed  Google Scholar 

  • Alexandre H, Mathieu B, Charpentier C (1996) Alteration in membrane fluidity and lipid composition, and modulation of H+-ATPase activity in Saccharomyces cerevisiae caused by decanoic acid. Microbiology 142:469–475

    CAS  PubMed  Google Scholar 

  • Alper H, Fischer C, Nevoigt E, Stephanopoulos G (2005) Tuning genetic control through promoter engineering. Proc Natl Acad Sci U S A 102:12678–12683

    CAS  PubMed  PubMed Central  Google Scholar 

  • Alper H, Moxley J, Nevoigt E, Fink GR, Stephanopoulos G (2006) Engineering yeast transcription machinery for improved ethanol tolerance and production. Science 314:1565–1568

    CAS  PubMed  Google Scholar 

  • Baganz F, Hayes A, Marren D, Gardner DCJ, Oliver SG (1997) Suitability of replacement markers for functional analysis studies in Saccharomyces cerevisiae. Yeast 13:1563–1573

    CAS  PubMed  Google Scholar 

  • Basso TO, Dario MG, Tonso A, Stambuk BU, Gombert AK (2010) Insufficient uracil supply in fully aerobic chemostat cultures of Saccharomyces cerevisiae leads to respiro-fermentative metabolism and double nutrient-limitation. Biotechnol Lett 32:973–977

    CAS  PubMed  Google Scholar 

  • Baumann L, Rajkumar AS, Morrissey JP, Boles E, Oreb M (2018) A yeast-based biosensor for screening of short- and medium-chain fatty acid production. ACS Synth Biol 7:2640–2646

    CAS  PubMed  Google Scholar 

  • Becker S, Schmoldt H-U, Adams TM, Wilhelm S, Kolmar H (2004) Ultra-high-throughput screening based on cell-surface display and fluorescence-activated cell sorting for the identification of novel biocatalysts. Curr Opin Biotechnol 15:323–329

    CAS  PubMed  Google Scholar 

  • Beopoulos A, Chardot T, Nicaud J-M (2009) Yarrowia lipolytica: a model and a tool to understand the mechanisms implicated in lipid accumulation. Biochimie 91:692–696

    CAS  PubMed  Google Scholar 

  • Besada-Lombana PB, Fernandez-Moya R, Fenster J, Da Silva NA (2017) Engineering Saccharomyces cerevisiae fatty acid composition for increased tolerance to octanoic acid. Biotechnol Bioeng 114:1531–1538

    CAS  PubMed  Google Scholar 

  • Black PN, DiRusso CC (2007) Yeast acyl-CoA synthetases at the crossroads of fatty acid metabolism and regulation. Biochim Biophys Acta 1771:286–298

    CAS  PubMed  Google Scholar 

  • Bocanegra JA, Scrutton NS, Perham RN (1993) Creation of an NADP-dependent pyruvate dehydrogenase multienzyme complex by protein engineering. Biochemistry 32:2737–2740

    CAS  PubMed  Google Scholar 

  • Brignole EJ, Smith S, Asturias FJ (2009) Conformational flexibility of metazoan fatty acid synthase enables catalysis. Nat Struct Mol Biol 16:190–197

    CAS  PubMed  PubMed Central  Google Scholar 

  • Buijs NA, Zhou YJ, Siewers V, Nielsen J (2015) Long-chain alkane production by the yeast Saccharomyces cerevisiae. Biotechnol Bioeng 112:1275–1279

    CAS  PubMed  Google Scholar 

  • Çakar ZP, Sauer U, Bailey JE (1999) Metabolic engineering of yeast: the perils of auxotrophic hosts. Biotechnol Lett 21:611–616

    Google Scholar 

  • Cardenas J, Da Silva NA (2016) Engineering cofactor and transport mechanisms in Saccharomyces cerevisiae for enhanced acetyl-CoA and polyketide biosynthesis. Metab Eng 36:80–89

    CAS  PubMed  Google Scholar 

  • Caspeta L, Chen Y, Ghiaci P, Feizi A, Buskov S, Hallström BM, Petranovic D, Nielsen J (2014) Altered sterol composition renders yeast thermotolerant. Science 346:75–78

    CAS  PubMed  Google Scholar 

  • Cernak P, Estrela R, Poddar S, Skerker JM, Cheng Y-F, Carlson AK, Chen B, Glynn VM, Furlan M, Ryan OW, Donnelly MK, Arkin AP, Taylor JW, Cate JHD (2018) Engineering Kluyveromyces marxianus as a robust synthetic biology platform host. MBio 9:1–16

    Google Scholar 

  • Chen B, Ling H, Chang MW (2013a) Transporter engineering for improved tolerance against alkane biofuels in Saccharomyces cerevisiae. Biotechnol Biofuels 6:21

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen Y, Daviet L, Schalk M, Siewers V, Nielsen J (2013b) Establishing a platform cell factory through engineering of yeast acetyl-CoA metabolism. Metab Eng 15:48–54

    CAS  PubMed  Google Scholar 

  • Chen B, Lee D-Y, Chang MW (2015) Combinatorial metabolic engineering of Saccharomyces cerevisiae for terminal alkene production. Metab Eng 31:53–61

    PubMed  Google Scholar 

  • Choi JW, Da Silva NA (2014) Improving polyketide and fatty acid synthesis by engineering of the yeast acetyl-CoA carboxylase. J Biotechnol 187:56–59

    CAS  PubMed  Google Scholar 

  • Clomburg JM, Vick JE, Blankschien MD, Rodríguez-Moyá M, Gonzalez R (2012) A synthetic biology approach to engineer a functional reversal of the β-oxidation cycle. ACS Synth Biol 1:541–554

    CAS  PubMed  Google Scholar 

  • Clomburg JM, Blankschien MD, Vick JE, Chou A, Kim S, Gonzalez R (2015) Integrated engineering of β-oxidation reversal and ω-oxidation pathways for the synthesis of medium chain ω-functionalized carboxylic acids. Metab Eng 28:202–212

    CAS  PubMed  Google Scholar 

  • Cottrell M, Viljoen BC, Kock JLF, Lategan PM (1986) The long-chain fatty acid compositions of species representing the genera Saccharomyces, Schwanniomyces and Lipomyces. Microbiology 132:2401–2403

    CAS  Google Scholar 

  • Curran KA, Karim AS, Gupta A, Alper HS (2013) Use of expression-enhancing terminators in Saccharomyces cerevisiae to increase mRNA half-life and improve gene expression control for metabolic engineering applications. Metab Eng 19:88–97

    CAS  PubMed  PubMed Central  Google Scholar 

  • d’Espaux L, Mendez-Perez D, Li R, Keasling JD (2015) Synthetic biology for microbial production of lipid-based biofuels. Curr Opin Chem Biol 29:58–65

    PubMed  Google Scholar 

  • d’Espaux L, Ghosh A, Runguphan W, Wehrs M, Xu F, Konzock O, Dev I, Nhan M, Gin J, Reider Apel A, Petzold CJ, Singh S, Simmons BA, Mukhopadhyay A, García Martín H, Keasling JD (2017) Engineering high-level production of fatty alcohols by Saccharomyces cerevisiae from lignocellulosic feedstocks. Metab Eng 42:115–125

    PubMed  Google Scholar 

  • Da Silva NA, Srikrishnan S (2012) Introduction and expression of genes for metabolic engineering applications in Saccharomyces cerevisiae. FEMS Yeast Res 12:197–214

    PubMed  Google Scholar 

  • David F, Nielsen J, Siewers V (2016) Flux control at the malonyl-CoA node through hierarchical dynamic pathway regulation in Saccharomyces cerevisiae. ACS Synth Biol 5:224–233

    CAS  PubMed  Google Scholar 

  • Davis López SA, Griffith DA, Choi B, Cate JHD, Tullman-Ercek D (2018) Evolutionary engineering improves tolerance for medium-chain alcohols in Saccharomyces cerevisiae. Biotechnol Biofuels 11:36

    Google Scholar 

  • de Jong BW, Shi S, Siewers V, Nielsen J (2014) Improved production of fatty acid ethyl esters in Saccharomyces cerevisiae through up-regulation of the ethanol degradation pathway and expression of the heterologous phosphoketolase pathway. Microb Cell Factories 13:39

    Google Scholar 

  • Dekishima Y, Lan EI, Shen CR, Cho KM, Liao JC (2011) Extending carbon chain length of 1-butanol pathway for 1-hexanol synthesis from glucose by engineered Escherichia coli. J Am Chem Soc 133:11399–11401

    CAS  PubMed  Google Scholar 

  • Dellomonaco C, Clomburg JM, Miller EN, Gonzalez R (2011) Engineered reversal of the β-oxidation cycle for the synthesis of fuels and chemicals. Nature 476:355–359

    CAS  PubMed  Google Scholar 

  • Deparis Q, Claes A, Foulquié-Moreno MR, Thevelein JM (2017) Engineering tolerance to industrially relevant stress factors in yeast cell factories. FEMS Yeast Res 17:861

    Google Scholar 

  • Dietrich JA, McKee AE, Keasling JD (2010) High-throughput metabolic engineering: advances in small-molecule screening and selection. Annu Rev Biochem 79:563–590

    CAS  PubMed  Google Scholar 

  • Dragosits M, Mattanovich D (2013) Adaptive laboratory evolution—principles and applications for biotechnology. Microb Cell Factories 12:64

    Google Scholar 

  • Eriksen DT, HamediRad M, Yuan Y, Zhao H (2015) Orthogonal fatty acid biosynthetic pathway improves fatty acid ethyl ester production in Saccharomyces cerevisiae. ACS Synth Biol 4:808–814

    CAS  PubMed  Google Scholar 

  • Feng X, Lian J, Zhao H (2015) Metabolic engineering of Saccharomyces cerevisiae to improve 1-hexadecanol production. Metab Eng 27:10–19

    CAS  PubMed  Google Scholar 

  • Fernandez-Moya R, Da Silva NA (2017) Engineering Saccharomyces cerevisiae for high-level synthesis of fatty acids and derived products. FEMS Yeast Res 17:87

    Google Scholar 

  • Fernandez-Moya R, Leber C, Cardenas J, Da Silva NA (2015) Functional replacement of the Saccharomyces cerevisiae fatty acid synthase with a bacterial type II system allows flexible product profiles. Biotechnol Bioeng 112:2618–2623

    CAS  PubMed  Google Scholar 

  • Foo JL, Susanto AV, Keasling JD, Leong SSJ, Chang MW (2017) Whole-cell biocatalytic and de novo production of alkanes from free fatty acids in Saccharomyces cerevisiae. Biotechnol Bioeng 114:232–237

    CAS  PubMed  Google Scholar 

  • Gajewski J, Pavlovic R, Fischer M, Boles E, Grininger M (2017) Engineering fungal de novo fatty acid synthesis for short chain fatty acid production. Nat Commun 8:14650

    PubMed  PubMed Central  Google Scholar 

  • Gibson BR, Lawrence SJ, Leclaire JPR, Powell CD, Smart KA (2007) Yeast responses to stresses associated with industrial brewery handling. FEMS Microbiol Rev 31:535–569

    CAS  PubMed  Google Scholar 

  • González-Ramos D, van den Broek M, van Maris AJA, Pronk JT, Daran J-MG (2013) Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation. Biotechnol Biofuels 6:48

    PubMed  PubMed Central  Google Scholar 

  • González-Ramos D, Gorter de Vries AR, Grijseels SS, van Berkum MC, Swinnen S, van den Broek M, Nevoigt E, Daran J-MG, Pronk JT, van Maris AJA (2016) A new laboratory evolution approach to select for constitutive acetic acid tolerance in Saccharomyces cerevisiae and identification of causal mutations. Biotechnol Biofuels 9:19

    Google Scholar 

  • Gossing M, Smialowska A, Nielsen J (2018) Impact of forced fatty acid synthesis on metabolism and physiology of Saccharomyces cerevisiae. FEMS Yeast Res 18:153

    Google Scholar 

  • Han L, Peng Y, Zhang Y, Chen W, Lin Y, Wang Q (2017) Designing and creating a synthetic omega oxidation pathway in Saccharomyces cerevisiae enables production of medium-chain α, ω-dicarboxylic acids. Front Microbiol 8:1123

    Google Scholar 

  • Hanscho M, Ruckerbauer DE, Chauhan N, Hofbauer HF, Krahulec S, Nidetzky B, Kohlwein SD, Zanghellini J, Natter K (2012) Nutritional requirements of the BY series of Saccharomyces cerevisiae strains for optimum growth. FEMS Yeast Res 12:796–808

    CAS  PubMed  Google Scholar 

  • Henritzi S, Fischer M, Grininger M, Oreb M, Boles E (2018) An engineered fatty acid synthase combined with a carboxylic acid reductase enables de novo production of 1-octanol in Saccharomyces cerevisiae. Biotechnol Biofuels 11:150

    PubMed  PubMed Central  Google Scholar 

  • Hettema EH, Tabak HF (2000) Transport of fatty acids and metabolites across the peroxisomal membrane. Biochim Biophys Acta 1486:18–27

    CAS  PubMed  Google Scholar 

  • Hettema EH, van Roermund CW, Distel B, van den Berg M, Vilela C, Rodrigues-Pousada C, Wanders RJ, Tabak HF (1996) The ABC transporter proteins Pat1 and Pat2 are required for import of long-chain fatty acids into peroxisomes of Saccharomyces cerevisiae. EMBO J 15:3813–3822

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hiltunen JK, Mursula AM, Rottensteiner H, Wierenga RK, Kastaniotis AJ, Gurvitz A (2003) The biochemistry of peroxisomal β-oxidation in the yeast Saccharomyces cerevisiae. FEMS Microbiol Rev 27:35–64

    CAS  PubMed  Google Scholar 

  • Hirasawa T, Yoshikawa K, Nakakura Y, Nagahisa K, Furusawa C, Katakura Y, Shimizu H, Shioya S (2007) Identification of target genes conferring ethanol stress tolerance to Saccharomyces cerevisiae based on DNA microarray data analysis. J Biotechnol 131:34–44

    CAS  PubMed  Google Scholar 

  • Hofbauer HF, Schopf FH, Schleifer H, Knittelfelder OL, Pieber B, Rechberger GN, Wolinski H, Gaspar ML, Kappe CO, Stadlmann J, Mechtler K, Zenz A, Lohner K, Tehlivets O, Henry SA, Kohlwein SD (2014) Regulation of gene expression through a transcriptional repressor that senses acyl-chain length in membrane phospholipids. Dev Cell 29:729–739

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hu Y, Zhu Z, Nielsen J, Siewers V (2018) Heterologous transporter expression for improved fatty alcohol secretion in yeast. Metab Eng 45:51–58

    CAS  PubMed  Google Scholar 

  • Jin Z, Wong A, Foo JL, Ng J, Cao Y-X, Chang MW, Yuan Y-J (2016) Engineering Saccharomyces cerevisiae to produce odd chain-length fatty alcohols. Biotechnol Bioeng 113:842–851

    CAS  PubMed  Google Scholar 

  • Johnson DR, Knoll LJ, Rowleyo N, Gordon JI (1994) Genetic analysis of the role of Saccharomyces cerevisiae acyl-CoA synthetase genes in regulating protein N-myristoylation. J Biol Chem 269(27):18037–18046. http://www.jbc.org/content/269/27/18037.full.pdf

    CAS  PubMed  Google Scholar 

  • Johnson AO, Gonzalez-Villanueva M, Wong L, Steinbüchel A, Tee KL, Xu P, Wong TS (2017) Design and application of genetically-encoded malonyl-CoA biosensors for metabolic engineering of microbial cell factories. Metab Eng 44:253–264

    CAS  PubMed  Google Scholar 

  • Kamisaka Y, Tomita N, Kimura K, Kainou K, Uemura H (2007) DGA1 (diacylglycerol acyltransferase gene) overexpression and leucine biosynthesis significantly increase lipid accumulation in the Δsnf2 disruptant of Saccharomyces cerevisiae. Biochem J 408:61–68

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kamisaka Y, Kimura K, Uemura H, Yamaoka M (2015) Addition of methionine and low cultivation temperatures increase palmitoleic acid production by engineered Saccharomyces cerevisiae. Appl Microbiol Biotechnol 99:201–210

    CAS  PubMed  Google Scholar 

  • Kaneda K, Imaizumi S, Yano I (1995) Distribution of C22-, C24- and C26-α-unit-containing mycolic acid homologues in mycobacteria. Microbiol Immunol 39:563–570

    CAS  PubMed  Google Scholar 

  • Kang M-K, Zhou YJ, Buijs NA, Nielsen J (2017) Functional screening of aldehyde decarbonylases for long-chain alkane production by Saccharomyces cerevisiae. Microb Cell Factories 16:320

    Google Scholar 

  • Kim S, Gonzalez R (2018) Selective production of decanoic acid from iterative reversal of β-oxidation pathway. Biotechnol Bioeng 115:1311–1320

    CAS  PubMed  Google Scholar 

  • Kim S, Clomburg JM, Gonzalez R (2015) Synthesis of medium-chain length (C6-C10) fuels and chemicals via β-oxidation reversal in Escherichia coli. J Ind Microbiol Biotechnol 42:465–475

    CAS  PubMed  Google Scholar 

  • Knappe J, Schacht J, Möckel W, Höpner T, Vetter H, Edenharder R (1969) Pyruvate formate-lyase reaction in Escherichia coli. The enzymatic system converting an inactive form of the lyase into the catalytically active enzyme. Eur J Biochem 11:316–327

    CAS  PubMed  Google Scholar 

  • Knoll LJ, Johnson DR, Gordon JI (1994) Biochemical studies of three Saccharomyces cerevisiae acyl-CoA synthetases, Faalp, FaaZp, and Faa3p. J Biol Chem 269:16348–16356

    CAS  PubMed  Google Scholar 

  • Kocharin K, Chen Y, Siewers V, Nielsen J (2012) Engineering of acetyl-CoA metabolism for the improved production of polyhydroxybutyrate in Saccharomyces cerevisiae. AMB Express 2:52

    PubMed  PubMed Central  Google Scholar 

  • Kocharin K, Siewers V, Nielsen J (2013) Improved polyhydroxybutyrate production by Saccharomyces cerevisiae through the use of the phosphoketolase pathway. Biotechnol Bioeng 110:2216–2224

    CAS  PubMed  Google Scholar 

  • Koopman F, Beekwilder J, Crimi B, van Houwelingen A, Hall RD, Bosch D, van Maris AJA, Pronk JT, Daran J-M (2012) De novo production of the flavonoid naringenin in engineered Saccharomyces cerevisiae. Microb Cell Factories 11:155

    CAS  Google Scholar 

  • Kozak BU, van Rossum HM, Luttik MAH, Akeroyd M, Benjamin KR, Wu L, de Vries S, Daran J-M, Pronk JT, van Maris AJA (2014a) Engineering acetyl coenzyme A supply: functional expression of a bacterial pyruvate dehydrogenase complex in the cytosol of Saccharomyces cerevisiae. MBio 5:e01696–e01614

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kozak BU, van Rossum HM, Benjamin KR, Wu L, Daran J-MG, Pronk JT, van Maris AJA (2014b) Replacement of the Saccharomyces cerevisiae acetyl-CoA synthetases by alternative pathways for cytosolic acetyl-CoA synthesis. Metab Eng 21:46–59

    CAS  PubMed  Google Scholar 

  • Kozak BU, van Rossum HM, Niemeijer MS, van Dijk M, Benjamin K, Wu L, Daran J-MG, Pronk JT, van Maris AJA (2016) Replacement of the initial steps of ethanol metabolism in Saccharomyces cerevisiae by ATP-independent acetylating acetaldehyde dehydrogenase. FEMS Yeast Res 16:fow006

    PubMed  PubMed Central  Google Scholar 

  • Krivoruchko A, Serrano-Amatriain C, Chen Y, Siewers V, Nielsen J (2013) Improving biobutanol production in engineered Saccharomyces cerevisiae by manipulation of acetyl-CoA metabolism. J Ind Microbiol Biotechnol 40:1051–1056

    CAS  PubMed  Google Scholar 

  • Krivoruchko A, Zhang Y, Siewers V, Chen Y, Nielsen J (2015) Microbial acetyl-CoA metabolism and metabolic engineering. Metab Eng 28:28–42

    CAS  PubMed  Google Scholar 

  • Kruis AJ, Gallone B, Jonker T, Mars AE, van Rijswijck IMH, JCM W-R, Smid EJ, Steensels J, Verstrepen KJ, SWM K, van der Oost J, Weusthuis RA (2018) Contribution of Eat1 and other alcohol acyltransferases to ester production in Saccharomyces cerevisiae. Front Microbiol 9:345

    Google Scholar 

  • Lafon-Lafourcade S, Geneix C, Ribéreau-Gayon P (1984) Inhibition of alcoholic fermentation of grape must by fatty acids produced by yeasts and their elimination by yeast ghosts. Appl Environ Microbiol 47:1246–1249

    CAS  PubMed  PubMed Central  Google Scholar 

  • Leber C, Da Silva NA (2014) Engineering of Saccharomyces cerevisiae for the synthesis of short chain fatty acids. Biotechnol Bioeng 111:347–358

    CAS  PubMed  Google Scholar 

  • Leber C, Polson B, Fernandez-Moya R, Da Silva NA (2015) Overproduction and secretion of free fatty acids through disrupted neutral lipid recycle in Saccharomyces cerevisiae. Metab Eng 28:54–62

    CAS  PubMed  Google Scholar 

  • Leber C, Choi JW, Polson B, Da Silva NA (2016) Disrupted short chain specific β-oxidation and improved synthase expression increase synthesis of short chain fatty acids in Saccharomyces cerevisiae. Biotechnol Bioeng 113:895–900

    CAS  PubMed  Google Scholar 

  • Lee ME, DeLoache WC, Cervantes B, Dueber JE (2015) A highly characterized yeast toolkit for modular, multipart assembly. ACS Synth Biol 4:975–986

    CAS  PubMed  Google Scholar 

  • Legras JL, Erny C, Le Jeune C, Lollier M, Adolphe Y, Demuyter C, Delobel P, Blondin B, Karst F (2010) Activation of two different resistance mechanisms in Saccharomyces cerevisiae upon exposure to octanoic and decanoic acids. Appl Environ Microbiol 76:7526–7535

    CAS  PubMed  PubMed Central  Google Scholar 

  • Leibundgut M, Maier T, Jenni S, Ban N (2008) The multienzyme architecture of eukaryotic fatty acid synthases. Curr Opin Struct Biol 18:714–725

    CAS  PubMed  Google Scholar 

  • Lennen RM, Pfleger BF (2013) Microbial production of fatty acid-derived fuels and chemicals. Curr Opin Biotechnol 24:1044–1053

    CAS  PubMed  Google Scholar 

  • Li X, Guo D, Cheng Y, Zhu F, Deng Z, Liu T (2014) Overproduction of fatty acids in engineered Saccharomyces cerevisiae. Biotechnol Bioeng 111:1841–1852

    CAS  PubMed  Google Scholar 

  • Li S, Si T, Wang M, Zhao H (2015) Development of a synthetic malonyl-CoA sensor in Saccharomyces cerevisiae for intracellular metabolite monitoring and genetic screening. ACS Synth Biol 4:1308–1315

    CAS  PubMed  Google Scholar 

  • Lian J, Zhao H (2015) Reversal of the β-oxidation cycle in Saccharomyces cerevisiae for production of fuels and chemicals. ACS Synth Biol 4:332–341

    CAS  PubMed  Google Scholar 

  • Lian J, Si T, Nair NU, Zhao H (2014) Design and construction of acetyl-CoA overproducing Saccharomyces cerevisiae strains. Metab Eng 24:139–149

    CAS  PubMed  Google Scholar 

  • Ling H, Chen B, Kang A, Lee J-M, Chang M (2013) Transcriptome response to alkane biofuels in Saccharomyces cerevisiae: identification of efflux pumps involved in alkane tolerance. Biotechnol Biofuels 6:95

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu H, Liu K, Yan M, Xu L, Ouyang P (2011) gTME for improved adaptation of Saccharomyces cerevisiae to corn cob acid hydrolysate. Appl Biochem Biotechnol 164:1150–1159

    CAS  PubMed  Google Scholar 

  • Liu P, Chernyshov A, Najdi T, Fu Y, Dickerson J, Sandmeyer S, Jarboe L (2013) Membrane stress caused by octanoic acid in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 97:3239–3251

    CAS  PubMed  Google Scholar 

  • Liu W, Zhang B, Jiang R (2017) Improving acetyl-CoA biosynthesis in Saccharomyces cerevisiae via the overexpression of pantothenate kinase and PDH bypass. Biotechnol Biofuels 10:97

    PubMed  PubMed Central  Google Scholar 

  • Lomakin IB, Xiong Y, Steitz TA (2007) The crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together. Cell 129:319–332

    PubMed  Google Scholar 

  • Mans R, Daran J-MG, Pronk JT (2018) Under pressure: evolutionary engineering of yeast strains for improved performance in fuels and chemicals production. Curr Opin Biotechnol 50:47–56

    CAS  PubMed  Google Scholar 

  • Marella ER, Holkenbrink C, Siewers V, Borodina I (2018) Engineering microbial fatty acid metabolism for biofuels and biochemicals. Curr Opin Biotechnol 50:39–46

    CAS  PubMed  Google Scholar 

  • Meadows AL, Hawkins KM, Tsegaye Y, Antipov E, Kim Y, Raetz L, Dahl RH, Tai A, Mahatdejkul-Meadows T, Xu L, Zhao L, Dasika MS, Murarka A, Lenihan J, Eng D, Leng JS, Liu C-L, Wenger JW, Jiang H, Chao L, Westfall P, Lai J, Ganesan S, Jackson P, Mans R, Platt D, Reeves CD, Saija PR, Wichmann G, Holmes VF, Benjamin K, Hill PW, Gardner TS, Tsong AE (2016) Rewriting yeast central carbon metabolism for industrial isoprenoid production. Nature 537:694–697

    CAS  PubMed  Google Scholar 

  • Membrillo-Hernandez J, Echave P, Cabiscol E, Tamarit J, Ros J, Lin EC (2000) Evolution of the adhE gene product of Escherichia coli from a functional reductase to a dehydrogenase. Genetic and biochemical studies of the mutant proteins. J Biol Chem 275:33869–33875

    CAS  PubMed  Google Scholar 

  • Michener JK, Thodey K, Liang JC, Smolke CD (2012) Applications of genetically-encoded biosensors for the construction and control of biosynthetic pathways. Metab Eng 14:212–222

    CAS  PubMed  Google Scholar 

  • Mukherjee K, Bhattacharyya S, Peralta-Yahya P (2015) GPCR-based chemical biosensors for medium-chain fatty acids. ACS Synth Biol 4:1261–1269

    CAS  PubMed  Google Scholar 

  • Nielsen J, Larsson C, van Maris A, Pronk J (2013) Metabolic engineering of yeast for production of fuels and chemicals. Curr Opin Biotechnol 24:398–404

    CAS  PubMed  Google Scholar 

  • NygÃ¥rd Y, Mojzita D, Toivari M, Penttilä M, Wiebe MG, Ruohonen L (2014) The diverse role of Pdr12 in resistance to weak organic acids. Yeast 31:219–232

    PubMed  Google Scholar 

  • Oelkers P, Tinkelenberg A, Erdeniz N, Cromley D, Billheimer JT, Sturley SL (2000) A lecithin cholesterol acyltransferase-like gene mediates diacylglycerol esterification in yeast. J Biol Chem 275:15609–15612

    CAS  PubMed  Google Scholar 

  • Oelkers P, Cromley D, Padamsee M, Billheimer JT, Sturley SL (2002) The DGA1 gene determines a second triglyceride synthetic pathway in yeast. J Biol Chem 277:8877–8881

    CAS  PubMed  Google Scholar 

  • Oh CS, Toke DA, Mandala S, Martin CE (1997) ELO2 and ELO3, homologues of the Saccharomyces cerevisiae ELO1 gene, function in fatty acid elongation and are required for sphingolipid formation. J Biol Chem 272:17376–17384

    CAS  PubMed  Google Scholar 

  • Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, Leavell MD, Tai A, Main A, Eng D, Polichuk DR, Teoh KH, Reed DW, Treynor T, Lenihan J, Jiang H, Fleck M, Bajad S, Dang G, Dengrove D, Diola D, Dorin G, Ellens KW, Fickes S, Galazzo J, Gaucher SP, Geistlinger T, Henry R, Hepp M, Horning T, Iqbal T, Kizer L, Lieu B, Melis D, Moss N, Regentin R, Secrest S, Tsuruta H, Vazquez R, Westblade LF, Xu L, Yu M, Zhang Y, Zhao L, Lievense J, Covello PS, Keasling JD, Reiling KK, Renninger NS, Newman JD (2013) High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496:528–532

    CAS  PubMed  Google Scholar 

  • Peralta-Yahya PP, Zhang F, del Cardayre SB, Keasling JD (2012) Microbial engineering for the production of advanced biofuels. Nature 488:320–328

    CAS  PubMed  Google Scholar 

  • Pfleger BF, Gossing M, Nielsen J (2015) Metabolic engineering strategies for microbial synthesis of oleochemicals. Metab Eng 29:1–11

    CAS  PubMed  Google Scholar 

  • Pham TK, Wright PC (2008) The proteomic response of Saccharomyces cerevisiae in very high glucose conditions with amino acid supplementation. J Proteome Res 7:4766–4774

    CAS  PubMed  Google Scholar 

  • Piper PW (1995) The heat shock and ethanol stress responses of yeast exhibit extensive similarity and functional overlap. FEMS Microbiol Lett 134:121–127

    CAS  PubMed  Google Scholar 

  • Pronk JT, Yde Steensma H, van Dijken JP (1996) Pyruvate metabolism in Saccharomyces cerevisiae. Yeast 12:1607–1633

    CAS  PubMed  Google Scholar 

  • Rigouin C, Gueroult M, Croux C, Dubois G, Borsenberger V, Barbe S, Marty A, Daboussi F, André I, Bordes F (2017) Production of medium chain Fatty acids by Yarrowia lipolytica: combining molecular design and TALEN to engineer the fatty acid synthase. ACS Synth Biol 6:1870–1879

    PubMed  Google Scholar 

  • Rodriguez S, Denby CM, van Vu T, Baidoo EEK, Wang G, Keasling JD (2016) ATP citrate lyase mediated cytosolic acetyl-CoA biosynthesis increases mevalonate production in Saccharomyces cerevisiae. Microb Cell Factories 15:169

    Google Scholar 

  • Royce LA, Yoon JM, Chen Y, Rickenbach E, Shanks JV, Jarboe LR (2015) Evolution for exogenous octanoic acid tolerance improves carboxylic acid production and membrane integrity. Metab Eng 29:180–188

    CAS  PubMed  Google Scholar 

  • Runguphan W, Keasling JD (2014) Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid-derived biofuels and chemicals. Metab Eng 21:103–113

    CAS  PubMed  Google Scholar 

  • Rupilius W, Ahma S (2006) The changing world of oleochemicals. Palm Oil Dev 44:21–28

    Google Scholar 

  • Sandoval CM, Ayson M, Moss N, Lieu B, Jackson P, Gaucher SP, Horning T, Dahl RH, Denery JR, Abbott DA, Meadows AL (2014) Use of pantothenate as a metabolic switch increases the genetic stability of farnesene producing Saccharomyces cerevisiae. Metab Eng 25:215–226

    CAS  PubMed  Google Scholar 

  • Santamauro F, Whiffin FM, Scott RJ, Chuck CJ (2014) Low-cost lipid production by an oleaginous yeast cultured in non-sterile conditions using model waste resources. Biotechnol Biofuels 7:34

    PubMed  PubMed Central  Google Scholar 

  • Sanz P (2003) Snf1 protein kinase: a key player in the response to cellular stress in yeast. Biochem Soc Trans 31:178–181

    CAS  PubMed  Google Scholar 

  • Sarria S, Kruyer NS, Peralta-Yahya P (2017) Microbial synthesis of medium-chain chemicals from renewables. Nat Biotechnol 35:1158–1166

    CAS  PubMed  Google Scholar 

  • Schadeweg V, Boles E (2016a) Increasing n-butanol production with Saccharomyces cerevisiae by optimizing acetyl-CoA synthesis, NADH levels and trans-2-enoyl-CoA reductase expression. Biotechnol Biofuels 9:1

    Google Scholar 

  • Schadeweg V, Boles E (2016b) n-Butanol production in Saccharomyces cerevisiae is limited by the availability of coenzyme A and cytosolic acetyl-CoA. Biotechnol Biofuels 9:1

    Google Scholar 

  • Schallmey M, Frunzke J, Eggeling L (2014) Looking for the pick of the bunch: high-throughput screening of producing microorganisms with biosensors. Curr Opin Biotechnol 26:148–154

    CAS  PubMed  Google Scholar 

  • Scharnewski M, Pongdontri P, Mora G, Hoppert M, Fulda M (2008) Mutants of Saccharomyces cerevisiae deficient in acyl-CoA synthetases secrete fatty acids due to interrupted fatty acid recycling. FEBS J 275:2765–2778

    CAS  PubMed  Google Scholar 

  • Schmidt JH (2015) Life cycle assessment of five vegetable oils. J Clean Prod 87:130–138

    Google Scholar 

  • Schweizer E, Hofmann J (2004) Microbial type I fatty acid synthases (FAS): major players in a network of cellular FAS systems. Microbiol Mol Biol Rev 68:501–517. Table of contents

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sekine T, Kawaguchi A, Hamano Y, Takagi H (2007) Desensitization of feedback inhibition of the Saccharomyces cerevisiae γ-glutamyl kinase enhances proline accumulation and freezing tolerance. Appl Environ Microbiol 73:4011–4019

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sheng J, Stevens J, Feng X (2016) Pathway compartmentalization in peroxisome of Saccharomyces cerevisiae to produce versatile medium chain fatty alcohols. Sci Rep 6:177

    Google Scholar 

  • Shi S, Valle-Rodríguez JO, Khoomrung S, Siewers V, Nielsen J (2012) Functional expression and characterization of five wax ester synthases in Saccharomyces cerevisiae and their utility for biodiesel production. Biotechnol Biofuels 5:7

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shi S, Valle-Rodríguez JO, Siewers V, Nielsen J (2014a) Engineering of chromosomal wax ester synthase integrated Saccharomyces cerevisiae mutants for improved biosynthesis of fatty acid ethyl esters. Biotechnol Bioeng 111:1740–1747

    CAS  PubMed  Google Scholar 

  • Shi S, Chen Y, Siewers V, Nielsen J (2014b) Improving production of malonyl coenzyme A-derived metabolites by abolishing Snf1-dependent regulation of Acc1. MBio 5:321

    Google Scholar 

  • Shi S, Ang EL, Zhao H (2018) In vivo biosensors: mechanisms, development, and applications. J Ind Microbiol Biotechnol 45:491–516

    CAS  PubMed  Google Scholar 

  • Shiba Y, Paradise EM, Kirby J, Ro D-K, Keasling JD (2007) Engineering of the pyruvate dehydrogenase bypass in Saccharomyces cerevisiae for high-level production of isoprenoids. Metab Eng 9:160–168

    CAS  PubMed  Google Scholar 

  • Shin G-H, Veen M, Stahl U, Lang C (2012) Overexpression of genes of the fatty acid biosynthetic pathway leads to accumulation of sterols in Saccharomyces cerevisiae. Yeast 29:371–383

    CAS  PubMed  Google Scholar 

  • Skjoedt ML, Snoek T, Kildegaard KR, Arsovska D, Eichenberger M, Goedecke TJ, Rajkumar AS, Zhang J, Kristensen M, Lehka BJ, Siedler S, Borodina I, Jensen MK, Keasling JD (2016) Engineering prokaryotic transcriptional activators as metabolite biosensors in yeast. Nat Chem Biol 12:951–958

    CAS  PubMed  Google Scholar 

  • Smidt O, Du Preez JC, Albertyn J (2012) Molecular and physiological aspects of alcohol dehydrogenases in the ethanol metabolism of Saccharomyces cerevisiae. FEMS Yeast Res 12:33–47

    PubMed  Google Scholar 

  • Stincone A, Prigione A, Cramer T, Wamelink MMC, Campbell K, Cheung E, Olin-Sandoval V, Grüning N-M, Krüger A, Tauqeer Alam M, Keller MA, Breitenbach M, Brindle KM, Rabinowitz JD, Ralser M (2015) The return of metabolism: biochemistry and physiology of the pentose phosphate pathway. Biol Rev Camb Philos Soc 90:927–963

    PubMed  Google Scholar 

  • Sumper M, Oesterhelt D, Riepertinger C, Lynen F (1969) Die Synthese verschiedener Carbonsäuren durch den Multienzymkomplex der Fettsäuresynthese aus Hefe und die Erklärung ihrer Bildung. Eur J Biochem 10:377–387

    CAS  PubMed  Google Scholar 

  • Suomalainen H, Keränen AJA (1963) The effect of biotin deficiency on the synthesis of fatty acids by yeast. Biochim Biophys Acta 70:493–503

    CAS  PubMed  Google Scholar 

  • Tang X, Chen WN (2015) Enhanced production of fatty alcohols by engineering the TAGs synthesis pathway in Saccharomyces cerevisiae. Biotechnol Bioeng 112:386–392

    CAS  PubMed  Google Scholar 

  • Tang X, Feng H, Chen WN (2013) Metabolic engineering for enhanced fatty acids synthesis in Saccharomyces cerevisiae. Metab Eng 16:95–102

    CAS  PubMed  Google Scholar 

  • Tang X, Feng L, Chen L, Chen WN (2017) Engineering Saccharomyces cerevisiae for efficient biosynthesis of fatty alcohols based on enhanced supply of free fatty acids. ACS Omega 2:3284–3290

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tehlivets O, Scheuringer K, Kohlwein SD (2007) Fatty acid synthesis and elongation in yeast. Biochim Biophys Acta 1771:255–270

    CAS  PubMed  Google Scholar 

  • Teixeira PG, Ferreira R, Zhou YJ, Siewers V, Nielsen J (2017) Dynamic regulation of fatty acid pools for improved production of fatty alcohols in Saccharomyces cerevisiae. Microb Cell Factories 16:1185

    Google Scholar 

  • Teo WS, Hee KS, Chang MW (2013) Bacterial FadR and synthetic promoters function as modular fatty acid sensor- regulators in Saccharomyces cerevisiae. Eng Life Sci 13:456–463

    CAS  Google Scholar 

  • Thompson RA, Trinh CT (2014) Enhancing fatty acid ethyl ester production in Saccharomyces cerevisiae through metabolic engineering and medium optimization. Biotechnol Bioeng 111:2200–2208

    CAS  PubMed  Google Scholar 

  • Toke DA, Martin CE (1996) Isolation and characterization of a gene affecting fatty acid elongation in Saccharomyces cerevisiae. J Biol Chem 271:18413–18422

    CAS  PubMed  Google Scholar 

  • Valle-Rodríguez JO, Shi S, Siewers V, Nielsen J (2014) Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid ethyl esters, an advanced biofuel, by eliminating non-essential fatty acid utilization pathways. Appl Energy 115:226–232

    Google Scholar 

  • van Roermund CW, Tabak HF, van den Berg M, Wanders RJ, Hettema EH (2000) Pex11p plays a primary role in medium-chain fatty acid oxidation, a process that affects peroxisome number and size in Saccharomyces cerevisiae. J Cell Biol 150:489–498

    PubMed  PubMed Central  Google Scholar 

  • van Roermund CW, Drissen R, van den Berg M, Ijlst L, Hettema EH, Tabak HF, Waterham HR, Wanders RJ (2001) Identification of a peroxisomal ATP carrier required for medium-chain fatty acid β-oxidation and normal peroxisome proliferation in Saccharomyces cerevisiae. Mol Cell Biol 21:4321–4329

    PubMed  PubMed Central  Google Scholar 

  • van Roermund CWT, Waterham HR, Ijlst L, Wanders RJA (2003) Fatty acid metabolism in Saccharomyces cerevisiae. Cell Mol Life Sci 60:1838–1851

    PubMed  Google Scholar 

  • van Rossum HM, Kozak BU, Niemeijer MS, Duine HJ, Luttik MAH, Boer VM, Kötter P, Daran J-MG, van Maris AJA, Pronk JT (2016a) Alternative reactions at the interface of glycolysis and citric acid cycle in Saccharomyces cerevisiae. FEMS Yeast Res 16:fow017

    PubMed  PubMed Central  Google Scholar 

  • van Rossum HM, Kozak BU, Pronk JT, van Maris AJA (2016b) Engineering cytosolic acetyl-coenzyme A supply in Saccharomyces cerevisiae: pathway stoichiometry, free-energy conservation and redox-cofactor balancing. Metab Eng 36:99–115

    PubMed  Google Scholar 

  • van Rossum HM, Kozak BU, Niemeijer MS, Dykstra JC, Luttik MAH, Daran J-MG, van Maris AJA, Pronk JT (2016c) Requirements for carnitine shuttle-mediated translocation of mitochondrial acetyl moieties to the yeast cytosol. MBio 7:517

    Google Scholar 

  • Viegas C (1997) Effects of low temperatures (9–33 °C) and pH (3.3–5.7) in the loss of Saccharomyces cerevisiae viability by combining lethal concentrations of ethanol with octanoic and decanoic acids. Int J Food Microbiol 34:267–277

    CAS  PubMed  Google Scholar 

  • Viegas CA, Sá-Correia I (1995) Toxicity of octanoic acid in Saccharomyces cerevisiae at temperatures between 8.5 and 30°C. Enzym Microb Technol 17:826–831

    CAS  Google Scholar 

  • Viegas CA, Rosa MF, Sá-Correia I, Novais JM (1989) Inhibition of yeast growth by octanoic and decanoic acids produced during ethanolic fermentation. Appl Environ Microbiol 55:21–28

    CAS  PubMed  PubMed Central  Google Scholar 

  • Viegas CA, Almeida PF, Cavaco M, Sá-Correia I (1998) The H(+)-ATPase in the plasma membrane of Saccharomyces cerevisiae is activated during growth latency in octanoic acid-supplemented medium accompanying the decrease in intracellular pH and cell viability. Appl Environ Microbiol 64:779–783

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vorapreeda T, Thammarongtham C, Cheevadhanarak S, Laoteng K (2012) Alternative routes of acetyl-CoA synthesis identified by comparative genomic analysis: involvement in the lipid production of oleaginous yeast and fungi. Microbiology (Reading, England) 158:217–228

    CAS  Google Scholar 

  • Waks Z, Silver PA (2009) Engineering a synthetic dual-organism system for hydrogen production. Appl Environ Microbiol 75:1867–1875

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang BL, Ghaderi A, Zhou H, Agresti J, Weitz DA, Fink GR, Stephanopoulos G (2014a) Microfluidic high-throughput culturing of single cells for selection based on extracellular metabolite production or consumption. Nat Biotechnol 32:473–478

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Chen H, Yu O (2014b) A plant malonyl-CoA synthetase enhances lipid content and polyketide yield in yeast cells. Appl Microbiol Biotechnol 98:5435–5447

    CAS  PubMed  Google Scholar 

  • Wang M, Li S, Zhao H (2016) Design and engineering of intracellular-metabolite-sensing/regulation gene circuits in Saccharomyces cerevisiae. Biotechnol Bioeng 113:206–215

    PubMed  Google Scholar 

  • Wattanachaisaereekul S, Lantz AE, Nielsen ML, Nielsen J (2008) Production of the polyketide 6-MSA in yeast engineered for increased malonyl-CoA supply. Metab Eng 10:246–254

    CAS  PubMed  Google Scholar 

  • Welch JW, Burlingame AL (1973) Very long-chain fatty acids in yeast. J Bacteriol 115:464–466

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wenning L, Yu T, David F, Nielsen J, Siewers V (2017) Establishing very long-chain fatty alcohol and wax ester biosynthesis in Saccharomyces cerevisiae. Biotechnol Bioeng 114:1025–1035

    CAS  PubMed  Google Scholar 

  • Williams TC, Xu X, Ostrowski M, Pretorius IS, Paulsen IT (2017) Positive-feedback, ratiometric biosensor expression improves high-throughput metabolite-producer screening efficiency in yeast. Synth Biol 2:1–13

    Google Scholar 

  • Wu C-C, Tsai Y-Y, Ohashi T, Misaki R, Limtong S, Fujiyama K (2018) Isolation of a thermotolerant Rhodosporidium toruloides DMKU3-TK16 mutant and its fatty acid profile at high temperature. FEMS Microbiol Lett 365(21). https://doi.org/10.1093/femsle/fny203

  • Xu P, Qiao K, Ahn WS, Stephanopoulos G (2016) Engineering Yarrowia lipolytica as a platform for synthesis of drop-in transportation fuels and oleochemicals. Proc Natl Acad Sci U S A 113:10848–10853

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xue S-J, Chi Z, Zhang Y, Li Y-F, Liu G-L, Jiang H, Hu Z, Chi Z-M (2018) Fatty acids from oleaginous yeasts and yeast-like fungi and their potential applications. Crit Rev Biotechnol 38:1049–1060

    CAS  PubMed  Google Scholar 

  • Yang H, Bard M, Bruner DA, Gleeson A, Deckelbaum RJ, Aljinovic G, Pohl TM, Rothstein R, Sturley SL (1996) Sterol esterification in yeast: a two-gene process. Science (New York, NY) 272:1353–1356

    CAS  Google Scholar 

  • Yoshikawa K, Tanaka T, Furusawa C, Nagahisa K, Hirasawa T, Shimizu H (2009) Comprehensive phenotypic analysis for identification of genes affecting growth under ethanol stress in Saccharomyces cerevisiae. FEMS Yeast Res 9:32–44

    CAS  PubMed  Google Scholar 

  • Yu A-Q, Pratomo Juwono NK, Leong SSJ, Chang MW (2014) Production of fatty acid-derived valuable chemicals in synthetic microbes. Front Bioeng Biotechnol 2:1219

    Google Scholar 

  • Yu A-Q, Pratomo Juwono NK, Foo JL, Leong SSJ, Chang MW (2016) Metabolic engineering of Saccharomyces cerevisiae for the overproduction of short branched-chain fatty acids. Metab Eng 34:36–43

    CAS  PubMed  Google Scholar 

  • Yu T, Zhou YJ, Wenning L, Liu Q, Krivoruchko A, Siewers V, Nielsen J, David F (2017) Metabolic engineering of Saccharomyces cerevisiae for production of very long chain fatty acid-derived chemicals. Nat Commun 8:15587

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yu T, Zhou YJ, Huang M, Liu Q, Pereira R, David F, Nielsen J (2018) Reprogramming yeast metabolism from alcoholic fermentation to lipogenesis. Cell 174:1549–1558.e14

    CAS  PubMed  Google Scholar 

  • Zhang F, Carothers JM, Keasling JD (2012) Design of a dynamic sensor-regulator system for production of chemicals and fuels derived from fatty acids. Nat Biotechnol 30:354–359

    CAS  PubMed  Google Scholar 

  • Zhang Y, Nielsen J, Liu Z (2018) Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid-derived hydrocarbons. Biotechnol Bioeng 110:87

    Google Scholar 

  • Zhou YJ, Buijs NA, Zhu Z, Gómez DO, Boonsombuti A, Siewers V, Nielsen J (2016a) Harnessing yeast peroxisomes for biosynthesis of fatty-acid-derived biofuels and chemicals with relieved side-pathway competition. J Am Chem Soc 138:15368–15377

    CAS  PubMed  Google Scholar 

  • Zhou YJ, Buijs NA, Zhu Z, Qin J, Siewers V, Nielsen J (2016b) Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories. Nat Commun 7:34

    Google Scholar 

  • Zhou YJ, Hu Y, Zhu Z, Siewers V, Nielsen J (2018) Engineering 1-alkene biosynthesis and secretion by dynamic regulation in yeast. ACS Synth Biol 7:584–590

    CAS  PubMed  Google Scholar 

  • Zhu Z, Zhou YJ, Kang M-K, Krivoruchko A, Buijs NA, Nielsen J (2017a) Enabling the synthesis of medium chain alkanes and 1-alkenes in yeast. Metab Eng 44:81–88

    CAS  PubMed  Google Scholar 

  • Zhu Z, Zhou YJ, Krivoruchko A, Grininger M, Zhao ZK, Nielsen J (2017b) Expanding the product portfolio of fungal type I fatty acid synthases. Nat Chem Biol 13:360–362

    CAS  PubMed  Google Scholar 

  • Zou Z, DiRusso CC, Ctrnacta V, Black PN (2002) Fatty acid transport in Saccharomyces cerevisiae. Directed mutagenesis of FAT1 distinguishes the biochemical activities associated with Fat1p. J Biol Chem 277:31062–31071

    CAS  PubMed  Google Scholar 

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Acknowledgments

L.B., F.W., and M.O. received funding from the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. 720824. S.B. received funding from the German Federal Ministry of Food and Agriculture following a decision of the German Bundestag under the Grant Number 22026315. The responsibility for the content of this publication lies with the authors. The authors thank Eckhard Boles for helpful comments on the manuscript.

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  1. Faculty of Biological Sciences, Institute of Molecular Biosciences, Goethe-University Frankfurt, Frankfurt, Germany

    Leonie Baumann, Florian Wernig, Sandra Born & Mislav Oreb

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  1. Leonie Baumann
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  2. Florian Wernig
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  4. Mislav Oreb
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Correspondence to Mislav Oreb .

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  1. TUM School of Life Sciences Weihenstephan, Holzforschung München – Fungal Biotechnology in Wood Science, Technische Universität München, Freising, Germany

    J. Philipp Benz

  2. Institut für Mikrobiologie, Department Biologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

    Kerstin Schipper

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Baumann, L., Wernig, F., Born, S., Oreb, M. (2020). Engineering Saccharomyces cerevisiae for Production of Fatty Acids and Their Derivatives. In: Benz, J.P., Schipper, K. (eds) Genetics and Biotechnology. The Mycota, vol 2. Springer, Cham. https://doi.org/10.1007/978-3-030-49924-2_14

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