Construction of a Part of a 3-Hydroxypropionate Cycle for Heterologous Polyketide Biosynthesis in Escherichia coli
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.
- Sponsoring Organization:
- USDOE Advanced Research Projects Agency - Energy (ARPA-E)
- DOE Contract Number:
- DE-AR0000091
- OSTI ID:
- 1211114
- Journal Information:
- Biochemistry, Vol. 51, Issue 49; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
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