title: Construction of a part of a 3-hydroxypropionate cycle for heterologous polyketide biosynthesis in Escherichia coli.
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.
authors.affiliation: QB3 Institute, University of California, Berkeley, CA 94270, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yuzawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Chiba
authors.forename: Leonard
authors.initials: L
authors.lastname: Katz
authors.forename: Jay D
authors.initials: JD
authors.lastname: Keasling
mesh_terms: D004926:Escherichia coli / Q000378:metabolism*; D019344:Lactic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D013058:Mass Spectrometry; D061065:Polyketides / Q000378:metabolism*
chemical_list: D061065:Polyketides; D019344:Lactic Acid; C031601:hydracrylic acid