Isolation and characterization of an Escherichia coli mutant fast-growing on nonanoic acid for improved azelaic acid production through a heterologous ω-oxidation pathway

Abstract

Azelaic acid, a medium-chain dicarboxylic acid (DCA) with nine carbons, has been used in plastics and acne medication. Azelaic acid is a natural product found in crops and animal products. Its value has been highlighted as a raw material for cosmetics because it has antibacterial and anti-inflammatory effect and a whitening effect on melasmas and freckles. In general, wild-type Escherichia coli cannot grow on the medium-chain fatty acids, probably because of its ineffective uptake. In this study, we constructed an E. coli MG1655 mutant with fadR deletion to unrepress gene expression of β-oxidation pathway. We obtained an E. coli strain that can grow faster than the wild type on nonanoic acid (C9 fatty acid), azelaic acid precursor, by evolutionary engineering and analyzed mutations that enable it to utilize efficiently by whole-genome sequencing. Then alkBGT-mediated ω-oxidation pathway system from Pseudomonas putida GPo1 expressed in the evolutionary engineered strain with fadE deletion to produce the C9 DCA. The mutant strain showed approximately 3-fold increased production of azelaic acid in comparison with wild type strain.