Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi, 832003, PR China.
Key Lab for Industrial Biocatalysis, Ministry of Education, Department of Chemical Engineering, Tsinghua University, Beijing, 100084, PR China.
Metab Eng. 2022 Mar;70:143-154. doi: 10.1016/j.ymben.2022.01.011. Epub 2022 Jan 25.
Plant flavonoids are secondary metabolites containing a benzo-γ-pyrone structure, which are widely present in plants and have a variety of physiological and pharmacological activities. However, current flavonoid production from plant extraction or chemical synthesis does not meet the requirements of green and sustainable development. Fortunately, microbial synthesis of flavonoids has shown the potential for large-scale production with the advantages of being controllable and environmentally friendly, and a variety of microorganisms have been developed as microbial cell factories (MCFs) to synthesize plant flavonoids owing to the feasibility of genetic manipulations. However, most of MCFs have not yet been commercialized and industrialized because of the challenges posed by unbalanced metabolic flux among various pathways and conflict between cell growth and production. Here, strategies for coping with the challenges are summarized in terms of enzymes, pathways, metabolic networks, host cells. And combined with protein structure prediction, de novo protein design, artificial intelligence (AI), biocatalytic retrosynthesis, and intelligent stress resistance, it provides new insights for the high efficient production of plant flavonoids and other plant natural products in MCFs.
植物类黄酮是含有苯并-γ-吡喃结构的次生代谢物，广泛存在于植物中，具有多种生理和药理活性。然而，目前从植物提取或化学合成的类黄酮生产方式不符合绿色和可持续发展的要求。幸运的是，由于遗传操作的可行性，微生物合成类黄酮显示出了大规模生产的潜力，具有可控和环保的优点，并且已经开发出多种微生物作为微生物细胞工厂（MCFs）来合成植物类黄酮。然而，由于各种途径之间代谢通量不平衡和细胞生长与生产之间的冲突等挑战，大多数 MCF 尚未实现商业化和工业化。在这里，从酶、途径、代谢网络、宿主细胞等方面总结了应对这些挑战的策略，并结合蛋白质结构预测、从头设计蛋白质、人工智能（AI）、生物催化反合成和智能抗应激，为 MCF 中植物类黄酮和其他植物天然产物的高效生产提供了新的见解。
