Improving coenzyme Q₈ production in Escherichia coli employing multiple strategies

Coenzyme Q (CoQ) is a medically valuable compound and a high yielding strain for CoQ will have several benefits for the industrial production of CoQ. To increase the CoQ₈ content of E. coli, we blocked the pathway for the synthesis of menaquinone by deleting the menA gene. The blocking of menaquinone pathway increased the CoQ₈ content by 81 % in E. coli (ΔmenA). To study the CoQ producing potential of E. coli, we employed previous known increasing strategies for systematic metabolic engineering. These include the supplementation with substrate precursors and the co-expression of rate-limiting genes. The co-expression of dxs-ubiA and the supplementation with substrate precursors such as pyruvate (PYR) and parahydroxybenzoic acid (pHBA) increased the content of CoQ₈ in E. coli (ΔmenA) by 125 and 59 %, respectively. Moreover, a 180 % increase in the CoQ₈ content in E. coli (ΔmenA) was realized by the combination of the co-expression of dxs-ubiA and the supplementation with PYR and pHBA. All in all, CoQ₈ content in E. coli increased 4.06 times by blocking the menaquinone pathway, dxs-ubiA co-expression and the addition of sodium pyruvate and parahydroxybenzoic acid to the medium. Results suggested a synergistic effect among different metabolic engineering strategies.