微生物细胞工厂生产化学品的研究进展——以几种典型小分子和大分子化学品为例

微生物细胞工厂的创制和优化改造是绿色生物制造的重要内容。基于构建高效微生物细胞工厂的主要使能技术及其新发展，以几种典型小分子和大分子化学品为例，综述了微生物细胞工厂生产化学品的研究进展。讨论了启动子工程、代谢流分析等经典的使能技术和CRISPR基因编辑、诱变耦合高通量筛选、基于人工智能的生物信息学等新技术对于微生物细胞工厂构筑的重要作用。分别以有机醇、有机酸、有机胺小分子和多糖、聚酯类生物大分子的微生物合成为例，分析了如何面向不同特点的产物分子，设计实施不同的基因改造策略，并概述了近年来代表性菌株的生产性能。进一步展望了未来微生物细胞工厂生产化学品的总体发展趋势和应用前景。

Progress for chemicals production via microbial cell factory: selecting several small molecules and macromolecular products as examples

The creation and optimization of microbial cell factories are an important part of green biological manufacturing. Based on introduction of important enabling technologies for construction of high-efficiency microbial cell factories, recent progress for producing representative chemicals via microbial cell factories was reviewed. First, the important roles of some key enabling technologies, including both the classical methods such as promoter engineering and metabolic flow analysis and the new developments such as CRISPR gene editing, mutagenesis-coupled high throughput screening and artificial-intelligence-based bioinformatics, were described and discussed. Next, taking organic alcohols, organic acids, organic amines, polysaccharides and polyesters as examples, diverse genetic strategies for developing superior engineered cell factories were highlighted, and the highest production levels of different representative products were also summarized. Finally, the overall development trend and prospect for production of bulk chemicals and macromolecules by microbial cell factories in the future are forecasted.