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. 2006 May 23:5:20.
doi: 10.1186/1475-2859-5-20.

Biosynthesis of isoprenoids, polyunsaturated fatty acids and flavonoids in Saccharomyces cerevisiae

Joseph A Chemler  1 , Yajun Yan, Mattheos A G Koffas
Affiliations

Biosynthesis of isoprenoids, polyunsaturated fatty acids and flavonoids in Saccharomyces cerevisiae

Joseph A Chemler et al. Microb Cell Fact. .

Abstract

Industrial biotechnology employs the controlled use of microorganisms for the production of synthetic chemicals or simple biomass that can further be used in a diverse array of applications that span the pharmaceutical, chemical and nutraceutical industries. Recent advances in metagenomics and in the incorporation of entire biosynthetic pathways into Saccharomyces cerevisiae have greatly expanded both the fitness and the repertoire of biochemicals that can be synthesized from this popular microorganism. Further, the availability of the S. cerevisiae entire genome sequence allows the application of systems biology approaches for improving its enormous biosynthetic potential. In this review, we will describe some of the efforts on using S. cerevisiae as a cell factory for the biosynthesis of high-value natural products that belong to the families of isoprenoids, flavonoids and long chain polyunsaturated fatty acids. As natural products are increasingly becoming the center of attention of the pharmaceutical and nutraceutical industries, the use of S. cerevisiae for their production is only expected to expand in the future, further allowing the biosynthesis of novel molecular structures with unique properties.

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Figures

Figure 1
Figure 1
Biosynthesis of isoprenoids by the mevalonate pathway. IPP: isopentenyl pyrophosphate; ERG10: acetoacetyl-CoA ligase; ERG13: 2-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase); HMG1 and HMG2: 2-hydroxy-3-methylglutaryl-CoA reductases; ERG12: mevalonate kinase; ERG8: phosphomevalonate kinase; MVD1: diphosphomevalonate decarboxylase; IDI1: isopentenyl pyrophosphate:dimethylallyl diphosphate isomerase; ERG20: farnesyl diphosphate synthase.
Figure 2
Figure 2
Taxol biosynthesis pathway. GGPPS: Genranylgenranyl diphosphate synthase; TS: taxadiene synthase; TYHa: taxadiene 5α-hydroxylase; TAT: taxa-4(20), 11(12)-dien-5a-ol-O-acetyltransferase; TYHb: taxane 10β-hydroxylase; TBT: taxane 2a-O-benzoyltransferase; DBAT: 10-deacetyl baccatin III-O-acetyltransferase. PAM: phenyalanine aminomutase. Multiple arrows indicate several as of yet undefined steps. Red text indicates a cytochrome P450 enzyme.
Figure 3
Figure 3
Carotenoid biosynthesis pathway. IPP: Isopentyl pyrophosphate; crtE: geranylgenranyl diphosphate synthase; crtB: phytoene synthase; crtI: phytoene desaturase; crtZ: β-carotene hydroxylase; crtX: zeaxanthin glucosylase; crtM: dehydrosqualene synthase; crtN: dehydrosqualene desaturase; crtEb: lycopene elongase; crtYe/Yf: heterodimeric decaprenoxanthin synthase.
Figure 4
Figure 4
Metabolic pathways of ω3 and ω6 fatty acids.
Figure 5
Figure 5
Flavonoid biosynthesis pathway. PAL: Phenylalanine ammonia-lyase; C4H: cinnamate-4-hydroxylase; 4CL: 4-coumaroyl:CoA-ligase; CHS: chalcone synthase; CHI: chalcone isomerase; FSI: flavone synthase; FSII: cytochrome P450 flavone synthase; IFS: cytochrome P450 isoflavone synthase; FHT: flavanone 3β-hydroxylase; DFR: dihydroflavonol 4-reductase; LAR: leucoanthocyanidin synthase; ANS: anthocyanidin synthase; 3GT: UDPG-flavonoid 3-O-glucosyl transferase. Red text indicates cytochrome P450 enzymes.
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