Rewiring FadR regulon for the selective production of ω-hydroxy palmitic acid from glucose in Escherichia coli.

摘要: Abstract ω-Hydroxy palmitic acid (ω-HPA) is a valuable compound for an ingredient of artificially synthesized ceramides and additive lubricants adhesives. Production such fatty derivative limited by chemical catalysis, but plausible biocatalysis. However, its low productivity issue, including formations unsaturated (UFA) byproducts in host cells, remains as hurdle toward industrial biological processes. In this study, to achieve selective high-level production ω-HPA from glucose Escherichia coli, FadR, native transcriptional regulator metabolism, regulon were engineered. First, FadR was co-expressed with thioesterase specificity enhance yield, considerable quantity UFAs also produced. order avoid the UFA caused fadR overexpression, rewired i) mutating consensus binding sites fabA or fabB, ii) integrating fabZ into fabI operon, iii) enhancing strength promoter. This approach led dramatic increases both proportion (48.3–83.0%) titer (377.8 mg/L 675.8 mg/L) acid, mainly due decrease synthesis. Introducing ω-hydroxylase, CYP153A35, engineered strain resulted highly (83.5 mg/L) accounting 87.5% total ω-hydroxy acids. Furthermore, strategies, enhancement CYP153A35 activity, expression transporter, supplementation triton X-100, iv) separation synthetic pathway two strains co-culture system, applied 401.0 mg/L production. For productions ω-HPA, rewiring regulation E. coli promising strategy develop process economical downstream processing.