Journal
FEMS YEAST RESEARCH
Volume 6, Issue 1, Pages 40-47Publisher
OXFORD UNIV PRESS
DOI: 10.1111/j.1567-1356.2005.00001.x
Keywords
polyketide synthase; metabolic engineering; heterologous expression; methylmalonyl-CoA
Funding
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R43GM056575, R44GM056575] Funding Source: NIH RePORTER
- NIGMS NIH HHS [GM 56575] Funding Source: Medline
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Polyketides are a diverse group of natural products with significance in human and veterinary medicine. Because polyketides are structurally complex molecules and fermentation is the most commercially viable route of production, a generic heterologous host system for high-level polyketide production is desirable. Saccharomyces cerevisiae has been shown to be an excellent production host for a simple polyketide, yielding 1.7 g of 6-methylsalicylic acid per liter of culture in unoptimized shake-flask fermentations. However, a barrier to the heterologous production of more complex 'modular' polyketides in S. cerevisiae is the lack of required polyketide precursor pathways. In this work, we describe the introduction into S. cerevisiae of pathways for the production of methylmalonyl-coenzyme A (CoA), a precursor for complex polyketides, by both propionyl-CoA-dependent and propionyl-CoA-independent routes. Furthermore, we demonstrate that the methylmalonyl-CoA produced in the engineered yeast strains is used in vivo for the production of a polyketide product, a triketide lactone.
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