加州大学Bradley S. Moore小组宣布他们的最新研究提出了动物色素眼黄素的生长偶联微生物生物合成。相关论文于2025年11月3日发表在《自然—生物技术》杂志上。

研究团队介绍了一种涉及反馈回路的生长耦合生物合成策略，其中切除的一碳（C1）片段被主题为细菌生长的驱动器，同时促进目标化合物的生物生产。这种广泛适用的即插即用策略通过在平台土壤细菌恶臭假单胞菌的5,10-亚甲基四氢叶酸营养不良菌中实现黄叶菌素生物合成来说明。在本设计中，黄胚素生产过程中释放的甲酸缓解了C1的缺乏，从而有效地将细菌生长与色素合成结合起来。适应性实验室进化简化了葡萄糖中黄原素的克级生物生产，建立了C1恢复作为一种通用的生物合成方法，以加速细菌天然产物的生物合成工程。

据悉，细菌中异源天然产物的工程途径已经取得了广泛的成功，但大多数方法的初始生产水平较低，需要大量的、重抗性的迭代菌株优化。黄胚素是一种结构复杂、可变色的动物共色素，具有材料和化妆品用途，但在微生物细胞工厂生产一直很困难。

附：英文原文

Title: Growth-coupled microbial biosynthesis of the animal pigment xanthommatin

Author: Bushin, Leah B., Alter, Tobias B., Alvn-Vargas, Mara V. G., Drr, Lara, Olson, Elina C., Avila, Mariah J., Volke, Daniel C., Puiggen, scar, Kim, Taehwan, Deravi, Leila F., Feist, Adam M., Nikel, Pablo I., Moore, Bradley S.

Issue&Volume: 2025-11-03

Abstract: Engineering heterologous natural product pathways in bacteria has achieved broad success but most approaches suffer from low initial production levels that require extensive, resource-heavy iterative strain optimization. Xanthommatin is a structurally complex, color-changing animal ommochrome with material and cosmetic applications, yet production in microbial cell factories has been difficult. Here, we introduce a growth-coupled biosynthetic strategy involving a feedback loop where an excised one-carbon (C1) moiety is used as a driver of bacterial growth, simultaneously boosting bioproduction of the target compound. This broadly applicable, plug-and-play strategy is illustrated by enabling xanthommatin biosynthesis in a 5,10-methylenetetrahydrofolate auxotroph of the platform soil bacterium Pseudomonas putida. In this design, formate released during xanthommatin production relieves the C1 deficiency, thereby effectively coupling bacterial growth to pigment synthesis. Adaptive laboratory evolution streamlined xanthommatin’s gram-scale bioproduction from glucose, establishing C1 restoration as a general biosynthetic approach to accelerate the engineering of natural product biosynthesis in bacteria.

DOI: 10.1038/s41587-025-02867-7

Source: https://www.nature.com/articles/s41587-025-02867-7