Improved production of long-chain α, ω-dicarboxylic acids by redox balancing in engineered Escherichia coli

Abstract

Long-chain α, ω-dicarboxylic acids (LDCAs, ≥ C12) are widely used as raw materials for preparing products such as perfumes, adhesives, polyamides, polyesters, and high quality lubricants. Biotechnology offers an innovative way to overcome the limitations and disadvantages of the chemical processes to make DCA from renewable raw materials such as fatty acids by whole cell biotransformation. We used a fusion protein chimera containing a CYP450 and a reductase domain for the terminal functionalization of fatty acids at the expense of a NADPH in addition to additional expenses of two NADP+ by the downstream reactions in the ω-oxidation pathway to obtain a DCA. It has been suggested that the inefficiency of cofactor regeneration by the resting cells may limit the biocatalytic reaction and reduce the final concentration of DCA. In the present study, we circumvent this limitation by co-synthesis of a sugar alcohol along with a DCA by a metabolically engineered Escherichia coli strain. The resulting strain finally achieved about 99% conversion of the substrate (C14 FA) in to the product (C14 DCA) with at least 4 fold increased product concentration than a control system.