合成类胡萝卜素细胞工厂的快速构建和定向进化

Rapid construction and directed evolution of cell factories for carotenoid biosynthesis

类胡萝卜素具有丰富的颜色和强抗氧化活性,这赋予了该类产品较高的商业价值,加速了该类产品合成路径在异源底盘中的构建进程,使之成为发展非理性设计策略的有效研究对象。本文主要针对微生物合成类胡萝卜素细胞工厂构建中的瓶颈问题,从增强合成类胡萝卜素前体GGPP的供给利用以及缓解各类胡萝卜素产品对微生物底盘细胞的胁迫压力两个角度,系统综述非理性设计策略对元件优化、模块适配和多维调控等路径构建优化方法的丰富,以及对不同尺度的DNA变异和适应性进化等底盘进化手段的推动作用。并从扩展类胡萝卜素合成底盘物种的多样性和丰富非天然类胡萝卜素产品结构的可获得性的需求出发,对构建合成该类产品微生物细胞工厂自动化和智能化的发展趋势进行展望。

Carotenoids have brilliant colors and strong antioxidant activity,which not only endow these compounds with high commercial value,but also accelerate the construction process for building efficient biosynthetic pathways in heterogeneous chassis.Carotenoids have become an ideal object to develop irrational design strategy.Here we critically review recent advances about carotenoid biosynthesis via irrational design strategies on pathway construction by parts optimization,modular compatibility,multidimensional regulation etc.,as well as chassis evolution by DNA mutation and adaptive evolution.These strategies aims to break the bottleneck of carotenoid biosynthesis through improving the supply and utilization of precursor GGPP as well as relieving the stress from carotenoid accumulation on microbiological chassis.Based on the demand of employing unconventional chassis and expanding carotenoid kingdom,we also propose the development of the construction strategies for carotenoid microbiological cell factories towards the automation and intellectualization.