Guangzhou Marine Laboratory Team Makes New Progress in Constructing Terpene Precursor Supply Chassis by Expressing an Actinomycetota-Derived MVA Pathway in Escherichia coli

Recently, the Marine Molecular Ecology and Chemical Ecology team at Guangzhou Marine Laboratory published a research paper titled "High-Level Terpene Production via a Novel Actinomycetota-Derived MVA Pathway in E. coli" in the top-tier journal Metabolic Engineering (CAS Q1, IF: 7.3). Both Prof. Pei-Yuan Qian and Dr. Jianwei Tang served as the corresponding authors, and Dr. Wenchao Liu was the first author. This study employed an innovative bioinformatics genomemining strategy to screen for highly efficient MVA pathway enzymes from over 25,000 actinomycetota genomes, and successfully constructed a high yield terpene precursor supply chassis in E. coli, providing a new platform for the industrial production of terpenoids. 

Terpenoids are a structurally diverse class of natural products with broad applications in pharmaceuticals, flavors, fragrances, and biofuels. However, insufficient terpene precursor supply in microbial hosts has long been a key bottleneck limiting their efficient heterologous biosynthesis. Although E. coli offers advantages such as rapid growth, ease of cultivation, and genetic tractability, its endogenous terpene precursor supply is extremely limited, severely restricting highlevel terpenoid production. The Guangzhou Marine Laboratory team aimed to break this bottleneck through metabolic engineering.

The research team first performed multi level global genome mining on 25,261 Actinomycetota genomes, identifying a series of MVA pathway enzymes with potentially high catalytic efficiency. Based on these enzyme components, they successfully constructed a genomically integrated MVA pathway in E. coli BL21(DE3) and developed two highly efficient terpene precursor synthesis chassis, ecMVA1 and ecMVA 2. To validate the functionality of this chassis platform, the team tested eight different terpene synthases (TSs), all of which successfully produced the corresponding terpenoids. In particular, fermentation of the artemisinin precursor amorphadiene in a 5L bioreactor reached a titer of 947.80 mg/L. This result demonstrates that the E. coli MVA chassis platform is not only suitable for laboratoryscale terpene synthase studies but also shows great potential for industrial applications. The computational screening strategy established in this study provides a new perspective for metabolic engineering and offers diverse chassis resources for the industrial production of terpenoidderived compounds.

This work was supported by the Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), the Hong Kong Special Administrative Region government, the Otto Poon Center for Climate Resilience and Sustainability of the Hong Kong University of Science and Technology, and the National Natural Science Foundation of China. The full paper can be accessed at:https://doi.org/10.1016/j.ymben.2026.102545