Engineering the production of the wood stilbene compound pinosylvin from lignin-derived trans-cinnamic acid in Escherichia coli by modulating malonyl-CoA pathway

Pinosylvin, a valuable stilbene compound found in Pinus heartwood, exhibits various bioactivities including antimicrobial, anti-inflammatory, and antitumor effects. Currently, pinosylvin is mostly obtained by direct plant extraction from woody plants, which is not environmentally friendly and difficult to meet the demand for commercial application. Herein, an efficient Escherichia coli cell factory was developed for the bioconversion of lignin-derived aromatic monomers into pinosylvin. Firstly, a better chassis strain was screened by combinatorial optimization. Then, to enhance the supply of the limiting precursor malonyl-CoA, the artificial small RNAs were designed to down-regulate fatty acid production, and the endogenous acetyl-CoA carboxylase was overexpressed. By engineering malonyl-CoA availability, resulting in a 1.3–2.2 fold increase in pinosylvin synthesis. Finally, 142.1 mg/L of pinosylvin was obtained in a 3-L bioreactor, achieving a reported highest yield of 1.09 mg/mg trans- cinnamic acid in the absence of cerulenin. This work provided an opportunity for the production of pinosylvin using a microbial cell factory and offered a reference for converting lignin-related aromatics into high-value chemicals. • Attained the highest pinosylvin yield from trans- cinnamic acid without cerulenin. • Addressed the issue of expensive cerulenin substitution. • Artificial sRNA-Hfq tool was used to down-regulate fatty acid synthesis pathway. • Overexpressing endogenous acetyl-CoA carboxylase increased pinosylvin production.