Biomaterial Database

Biosynthesis of Long-Chain ω-Hydroxy Fatty Acids by Engineered Saccharomyces cerevisiae. 2019

Jingjing Liu, and Chuanbo Zhang, and Wenyu Lu

School of Chemical Engineering and Technology , Tianjin University , Tianjin 300072 , P. R. China.

Long-chain hydroxy fatty acids (HFAs) are rare in nature but have many promising industrial applications. In this study, we developed a biosynthesis method to produce long-chain ω-hydroxy fatty acids. Through disruption of the acyl-CoA synthetases FAA1 and FAA4 and the fatty acyl-CoA oxidase POX1, a Saccharomyces cerevisiae strain was engineered to accumulate free fatty acids (FFAs). Subsequently, the cytochrome P450 monooxygenase CYP52M1 from Starmerella bombicola was introduced to convert FFAs to HFAs, leading to the production of C16 and C18 HFAs at the ω or ω-1 positions. Next, CYP52M1 was reconstituted with the homologous reductase S. bombicola CPR and the heterologous reductase Arabidopsis thaliana cytochrome P450 reductase. The results showed that the CYP52M1-AtCPR1 system significantly increased the hydroxylation in FFA. Moreover, a self-sufficient P450 enzyme system was constructed to achieve higher transformation efficiency. Finally, fed-batch fermentation yielded as much as 347 ± 9.2 mg/L ω-HFAs.

UI	MeSH Term	Description	Entries
D003066	Coenzyme A Ligases	Enzymes that catalyze the formation of acyl-CoA derivatives. EC 6.2.1.	Acyl CoA Synthetase,Acyl CoA Synthetases,Acyl Coenzyme A Synthetase,Acyl Coenzyme A Synthetases,Coenzyme A Ligase,Coenzyme A Synthetase,Coenzyme A Synthetases,Acid-Thiol Ligases,Co A Ligases,A Ligase, Coenzyme,A Synthetase, Coenzyme,Acid Thiol Ligases,CoA Synthetase, Acyl,CoA Synthetases, Acyl,Ligase, Coenzyme A,Ligases, Acid-Thiol,Ligases, Co A,Ligases, Coenzyme A,Synthetase, Acyl CoA,Synthetase, Coenzyme A,Synthetases, Acyl CoA,Synthetases, Coenzyme A
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D005227	Fatty Acids	Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)	Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids
D005285	Fermentation	Anaerobic degradation of GLUCOSE or other organic nutrients to gain energy in the form of ATP. End products vary depending on organisms, substrates, and enzymatic pathways. Common fermentation products include ETHANOL and LACTIC ACID.	Fermentations
D006900	Hydroxylation	Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)	Hydroxylations
D012441	Saccharomyces cerevisiae	A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.	Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker
D060847	Metabolic Engineering	Methods and techniques used to genetically modify cells' biosynthetic product output and develop conditions for growing the cells as BIOREACTORS.	Engineering, Metabolic
D029701	Saccharomyces cerevisiae Proteins	Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.	Baker's Yeast Proteins,S cerevisiae Proteins