Synthesis of polyhydroxyalkanoates from glucose that contain medium-chain-length monomers via the reversed fatty acid β-oxidation cycle in Escherichia coli

Polyhydroxyalkanoates that contain the medium-chain-length monomers (mcl-PHAs) have a wide range of applications owing to their superior physical and mechanical properties. A challenge to synthesize such mcl-PHAs from unrelated and renewable sources is exploiting the efficient metabolic pathways that lead to the formation of precursor (R)-3-hydroxyacyl-CoA. Here, by engineering the reversed fatty acid β-oxidation cycle, we were able to synthesize mcl-PHAs in Escherichia coli directly from glucose. After deletion of the major thioesterases, the engineered E. coli produced 6.62wt% of cell dry weight mcl-PHA heteropolymers. Furthermore, when a low-substrate-specificity PHA synthase from Pseudomonas stutzeri 1317 was employed, recombinant E. coli synthesized 12.10wt% of cell dry weight scl–mcl PHA copolymers, of which 21.18mol% was 3-hydroxybutyrate and 78.82mol% was medium-chain-length monomers. The reversed fatty acid β-oxidation cycle offered an efficient metabolic pathway for mcl-PHA biosynthesis in E. coli and can be further optimized. •The first synthesis of mcl-PHA directly from glucose via the reversed fatty acid β-oxidation.•Obtaining various types of PHAs which are composed of monomers 4-14 carbons.•The scl-mcl PHA accumulation up to 12.1 wt% or 786.50 mg l-1 in batch cultivation.