PMID:23181847

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Citation

Yuzawa, S, Chiba, N, Katz, L and Keasling, JD (2012) Construction of a part of a 3-hydroxypropionate cycle for heterologous polyketide biosynthesis in Escherichia coli. Biochemistry 51:9779-81

Abstract

Polyketides, an important class of natural products with complex chemical structures, are widely used as antibiotics and other pharmaceutical agents. A clear barrier to heterologous polyketide biosynthesis in Escherichia coli is the lack of (2S)-methylmalonyl-CoA, a common substrate of multimodular polyketide synthases. Here we report a route for synthesizing (2S)-methylmalonyl-CoA from malonyl-CoA with a 3-hydroxypropionate cycle in thermoacidophilic crenarchaeon. The engineered E. coli strain produced both propionyl-CoA and methylmalonyl-CoA at intracellular levels similar to those of acetyl-CoA and succinyl-CoA, respectively. This approach may open a way to produce a variety of polyketide drugs in E. coli from renewable carbon sources.

Links

PubMed Online version:10.1021/bi301414q

Keywords

Escherichia coli/metabolism; Lactic Acid/analogs & derivatives; Lactic Acid/metabolism; Mass Spectrometry; Polyketides/metabolism

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