Overproduction and secretion of free fatty acids through disrupted neutral lipid recycle in Saccharomyces cerevisiae

Metabolic Engineering

Volumn 28, Issue , 2015, Pages 54-62

  Leber, Christopher ^a   Polson, Brian ^a   Fernandez Moya, Ruben ^a   Da Silva, Nancy A ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Acyl CoA synthetase; Free fatty acids; Lipase; Lipid droplet; Saccharomyces cerevisiae; oxidation

Indexed keywords

DROPS; ENZYME ACTIVITY; GENES; GLYCEROL; LIPASES; YEAST;

ACYL-COA SYNTHETASE; BIOSYNTHETIC PATHWAY; DIACYLGLYCEROL ACYLTRANSFERASES; ENVIRONMENTAL CONCERNS; FREE FATTY ACID; INTRACELLULAR PROCESS; LIPID DROPLETS; TRIACYLGLYCEROL LIPASE;

FATTY ACIDS;

CARBON; DIACYLGLYCEROL ACYLTRANSFERASE; DIACYLGLYCEROL ACYLTRANSFERASE 1; FAT DROPLET; FATTY ACID; LIPID; LONG CHAIN FATTY ACID COENZYME A LIGASE; TRIACYLGLYCEROL LIPASE; TRIACYLGLYCEROL LIPASE 1; TRIACYLGLYCEROL LIPASE 3; TRIACYLGLYCEROL LIPASE 5; UNCLASSIFIED DRUG; SACCHAROMYCES CEREVISIAE PROTEIN;

ACID SECRETION; ARE1 GENE; ARTICLE; DNA SEQUENCE; ENZYME ANALYSIS; FAA1 GENE; FAA4 GENE; FAT1 GENE; FATTY ACID OXIDATION; FATTY ACID TRANSPORT; GENE; GENE DISRUPTION; GENE INACTIVATION; KNOCKOUT GENE; LIPID ANALYSIS; NONHUMAN; SACCHAROMYCES CEREVISIAE; ULTRAVIOLET RADIATION; GENE SILENCING; GENETICS; LIPID METABOLISM; METABOLISM; SECRETION (PROCESS);

SACCHAROMYCES CEREVISIAE;

FATTY ACIDS; GENE KNOCKDOWN TECHNIQUES; LIPID METABOLISM; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS;

EID: 84920135708     PISSN: 10967176     EISSN: 10967184     Source Type: Journal    
DOI: 10.1016/j.ymben.2014.11.006     Document Type: Article

References (41)

1. Amberg D., Burke D., Strathern J. Methods in Yeast Genetics 2005, Cold Spring Harbor Laboratory Press, New York.
2. Athenstaedt K., Daum G. YMR313c/TGL3 encodes a novel triacylglycerol lipase located in lipid particles of Saccharomyces cerevisiae. J. Biol. Chem. 2003, 278:23317-23323. 10.1074/jbc.M302577200.
3. Athenstaedt K., Daum G. Tgl4p and Tgl5p, two triacylglycerol lipases of the yeast Saccharomyces cerevisiae are localized to lipid particles. J. Biol. Chem. 2005, 280:37301-37309. 10.1074/jbc.M507261200.
4. Black P.N., DiRusso C.C. Yeast acyl-CoA synthetases at the crossroads of fatty acid metabolism and regulation. Biochim. Biophys. Acta 2007, 1771:286-298. 10.1016/j.bbalip.2006.05.003.
5. Blazeck J., Hill A., Liu L., Knight R., Miller J., Pan A., Otoupal P., Alper H.S. Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production. Nat. Commun. 2014, 5:3131. 10.1038/ncomms4131.
6. Bligh E.G., Dyer W.J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 1959, 37:911-917. 10.1139/o59-099.
7. Chen L., Zhang J., Lee J., Chen W. Enhancement of free fatty acid production in Saccharomyces cerevisiae by control of fatty acyl-CoA metabolism. Appl. Microbiol. Biotechnol. 2014, 98:6739-6750. 10.1007/s00253-014-5758-8.
8. Fang F., Salmon K., Shen M.W.Y., Aeling K.A., Ito E., Irwin B., Tran U.P.C., Hatfield G.W., Da Silva N.A., Sandmeyer S. A vector set for systematic metabolic engineering in Saccharomyces cerevisiae. Yeast 2011, 28:123-136. 10.1002/yea.1824.
9. Gibson D.G., Young L., Chuang R., Venter J.C., Hutchison C.A., Smith H.O. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat. Methods 2009, 6:343-345. 10.1038/nmeth.1318.
10. Henry S.A., Kohlwein S.D., Carman G.M. Metabolism and regulation of glycerolipids in the yeast Saccharomyces cerevisiae. Genetics 2012, 190:317-349. 10.1534/genetics.111.130286.
11. Hiltunen J.K., Mursula A.M., Rottensteiner H., Wierenga R.K., Kastaniotis A.J., Gurvitz A. The biochemistry of peroxisomal β-oxidation in the yeast Saccharomyces cerevisiae. FEMS Microbiol. Rev. 2003, 27:35-64. 10.1016/S0168-6445(03)00017-2.
12. Hoskins, L., July 5th, 2000. Yeast Transformation (high efficiency). Fred Hutchinson Cancer Research Center. Retrieved September 6th, 2012, from . http://labs.fhcrc.org/hahn/Methods/genetic_meth/dmso_yeast_transform.html.
13. Jandrositz A., Petschnigg J., Zimmermann R., Natter K., Scholze H., Hermetter A., Kohlwein S.D., Leber R. The lipid droplet enzyme Tgl1p hydrolyzes both steryl esters and triglycerides in the yeast Saccharomyces cerevisiae. Biochim. Biophys. Acta 2005, 1735:50-58. 10.1016/j.bbalip.2005.04.005.
14. Kamisaka Y., Kimura K., Uemura H., Yamaoka M. Overexpression of the active diacylglycerol acyltransferase variant transforms Saccharomyces cerevisiae into an oleaginous yeast. Appl. Microbiol. Biotechnol. 2013, 97:7345-7355. 10.1007/s00253-013-4915-9.
15. Klug L., Daum G. Yeast lipid metabolism at a glance. FEMS Yeast Res. 2014, 14:369-388. 10.1111/1567-1364.12141.
16. Koch B., Schmidt C., Daum G. Storage lipids of yeasts: a survey of nonpolar lipid metabolism in Saccharomyces cerevisiae, Pichia pastoris, and Yarrowia lipolytica. FEMS Microbiol. Rev. 2014, 1-24. 10.1111/1574-6976.12069.
17. Köffel R., Tiwari R., Falquet L., Schneiter R. The Saccharomyces cerevisiae YLL012/YEH1, YLR020/YEH2, and TGL1 genes encode a novel family of membrane-anchored lipases that are required for steryl ester hydrolysis. Mol. Cell. Biol. 2005, 25:1655-1668. 10.1128/MCB.25.5.1655-1668.2005.
18. Kohlwein S.D., Veenhuis M., van der Klei I.J. Lipid droplets and peroxisomes: key players in cellular lipid homeostasis or a matter of fat-store 'em up or burn 'em down. Genetics 2013, 193:1-50. 10.1534/genetics.112.143362.
19. Leber C., Da Silva N.A. Engineering of Saccharomyces cerevisiae for the synthesis of short chain fatty acids. Biotechnol. Bioeng. 2014, 111:347-358. 10.1002/bit.25021.
20. Lennen R.M., Braden D.J., West R.A., Dumesic J.A., Pfleger B.F. A process for microbial hydrocarbon synthesis: overproduction of fatty acids in Escherichia coli and catalytic conversion to alkanes. Biotechnol. Bioeng. 2010, 106:193-202. 10.1002/bit.22660.
21. Li X., Guo D., Cheng Y., Zhu F., Deng Z., Liu T. Overproduction of fatty acids in engineered Saccharomyces cerevisiae. Biotechnol. Bioeng. 2014, 111:1841-1852. 10.1002/bit.25239.
22. Lian J., Zhao H. Reversal of the β-oxidation cycle in Saccharomyces cerevisiae for production of fuels and chemicals. ACS Synth. Biol. 2014, 10.1021/sb500243c.
23. Liu H., Yu C., Feng D., Cheng T., Meng X., Liu W., Zou H., Xian M. Production of extracellular fatty acid using engineered Escherichia coli. Microb. Cell Factories 2012, 11:41. 10.1186/1475-2859-11-41.
24. Oelkers P., Cromley D., Padamsee M., Billheimer J.T., Sturley S.L. The DGA1 gene determines a second triglyceride synthetic pathway in yeast. J. Biol. Chem. 2002, 277:8877-8881. 10.1074/jbc.M111646200.
25. Peralta-Yahya P.P., Zhang F., del Cardayre S.B., Keasling J.D. Microbial engineering for the production of advanced biofuels. Nature 2012, 488:320-328. 10.1038/nature11478.
26. Ploier B., Scharwey M., Koch B., Schmidt C., Schatte J., Rechberger G., Kollroser M., Hermetter A., Daum G. Screening for hydrolytic enzymes reveals Ayr1p as a novel triacylglycerol lipase in Saccharomyces cerevisiae. J. Biol. Chem. 2013, 288:36061-36072. 10.1074/jbc.M113.509927.
27. Runguphan W., Keasling J.D. Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid-derived biofuels and chemicals. Metab. Eng. 2014, 21:103-113. 10.1016/j.ymben.2013.07.003.
28. Sambrook J., Russell D. Molecular Cloning: A Laboratory Manual 2001, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. 3rd ed.
29. Sandager L., Gustavsson M.H., Ståhl U., Dahlqvist A., Wiberg E., Banas A., Lenman M., Ronne H., Stymne S. Storage lipid synthesis is non-essential in yeast. J. Biol. Chem. 2002, 277:6478-6482. 10.1074/jbc.M109109200.
30. Scharnewski M., Pongdontri P., Mora G., Hoppert M., Fulda M. Mutants of Saccharomyces cerevisiae deficient in acyl-CoA synthetases secrete fatty acids due to interrupted fatty acid recycling. FEBS J. 2008, 275:2765-2778. 10.1111/j.1742-4658.2008.06417.x.
31. Schirmer A., Rude M.A., Li X., Popova E., del Cardayre S.B. Microbial biosynthesis of alkanes. Science 2010, 329:559-562. 10.1126/science.1187936.
32. Schmidt C., Athenstaedt K., Koch B., Ploier B., Daum G. Regulation of the yeast triacylglycerol lipase Tgl3p by formation of nonpolar lipids. J. Biol. Chem. 2013, 288:19939-19948. 10.1074/jbc.M113.459610.
33. Schweizer E., Hofmann J. Microbial type I fatty acid synthases (FAS): major players in a network of cellular FAS systems. Microbiol. Mol. Biol. Rev. 2004, 68:501-517. 10.1128/MMBR.68.3.501-517.2004.
34. Shen M.W.Y., Fang F., Sandmeyer S., Da Silva N.A. Development and characterization of a vector set with regulated promoters for systematic metabolic engineering in Saccharomyces cerevisiae. Yeast 2012, 29:495-503. 10.1002/yea.2930.
35. Steen E.J., Kang Y., Bokinsky G., Hu Z., Schirmer A., McClure A., Del Cardayre S.B., Keasling J.D. Microbial production of fatty-acid-derived fuels and chemicals from plant biomass. Nature 2010, 463:559-562. 10.1038/nature08721.
36. Tehlivets O., Scheuringer K., Kohlwein S.D. Fatty acid synthesis and elongation in yeast. Biochim. Biophys. Acta 2007, 1771:255-270. 10.1016/j.bbalip.2006.07.004.
37. Valle-Rodríguez J.O., Shi S., Siewers V., Nielsen J. 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 2014, 115:226-232. 10.1016/j.apenergy.2013.10.003.
38. Varman A.M., He L., You L., Hollinshead W., Tang Y.J. Elucidation of intrinsic biosynthesis yields using 13C-based metabolism analysis. Microb. Cell Factories 2014, 13:42. 10.1186/1475-2859-13-42.
39. Yang H., Cromley D., Wang H., Billheimer J.T., Sturley S.L. Functional expression of a cDNA to human acyl-coenzyme A:cholesterol acyltransferase in yeast. J. Biol. Chem. 1997, 272:3980-3985. 10.1074/jbc.272.7.3980.
40. Zhang X., Li M., Agrawal A., San K.-Y. Efficient free fatty acid production in Escherichia coli using plant acyl-ACP thioesterases. Metab. Eng. 2011, 13:713-722. 10.1016/j.ymben.2011.09.007.
41. Zweytick D., Leitner E., Kohlwein S.D., Yu C., Rothblatt J., Daum G. Contribution of Are1p and Are2p to steryl ester synthesis in the yeast Saccharomyces cerevisiae. Eur. J. Biochem. 2000, 267:1075-1082. 10.1046/j.1432-1327.2000.01103.x.