Yu Zhi-Pu, An Chunyan, Yao Yongpeng, Wang Chang-Yun, Sun Zhoutong, Cui Chengsen, Liu Ling, Gao Shu-Shan
Key Laboratory of Marine Drugs, The Ministry of Education of China, Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, PR China.
Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266003, PR China.
Synth Syst Biotechnol. 2022 Aug 20;7(4):1126-1132. doi: 10.1016/j.synbio.2022.08.003. eCollection 2022 Dec.
Microbial cell factories (MCFs) and cell-free systems (CFSs) are generally considered as two unrelated approaches for the biosynthesis of biomolecules. In the current study, two systems were combined together for the overproduction of agroclavine (AC), a structurally complex ergot alkaloid. The whole biosynthetic pathway for AC was split into the early pathway and the late pathway at the point of the FAD-linked oxidoreductase EasE, which was reconstituted in an MCF () and a four-enzyme CFS, respectively. The final titer of AC of this combined system is 1209 mg/L, which is the highest one that has been reported so far, to the best of our knowledge. The development of such a combined route could potentially avoid the limitations of both MCF and CFS systems, and boost the production of complex ergot alkaloids with polycyclic ring systems.
微生物细胞工厂（MCFs）和无细胞系统（CFSs）通常被认为是生物分子生物合成的两种不相关方法。在本研究中，将这两种系统结合在一起用于过量生产农业麦角碱（AC），这是一种结构复杂的麦角生物碱。AC的整个生物合成途径在与黄素腺嘌呤二核苷酸（FAD）相关的氧化还原酶EasE处被分为早期途径和晚期途径，该酶分别在微生物细胞工厂（ ）和四酶无细胞系统中进行了重组。据我们所知，这个组合系统中AC的最终产量为1209mg/L，是迄今为止报道的最高产量。这种组合途径的开发可能会避免微生物细胞工厂和无细胞系统的局限性，并提高具有多环系统的复杂麦角生物碱的产量。
