Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China.
Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, PR China; CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, PR China; Dalian Key Laboratory of Energy Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, PR China.
Metab Eng. 2023 Mar;76:225-231. doi: 10.1016/j.ymben.2023.02.008. Epub 2023 Feb 22.
Bioproduction of natural products via microbial cell factories is a promising alternative to traditional plant extraction. Recently, nonconventional microorganisms have emerged as attractive chassis hosts for biomanufacturing. One such microorganism, Ogataea polymorpha is an industrial yeast used for protein expression with numerous advantages, such as thermal-tolerance, a wide substrate spectrum and high-density fermentation. Here, we systematically rewired the cellular metabolism of O. polymorpha to achieve high-level production of the sesquiterpenoid β-elemene by optimizing the mevalonate pathway, enhancing the supply of NADPH and acetyl-CoA, and downregulating competitive pathways. The engineered strain produced 509 mg/L and 4.7 g/L of β-elemene under batch and fed-batch fermentation, respectively. Therefore, this study identified the potential industrial application of O. polymorpha as a good microbial platform for producing sesquiterpenoids.
通过微生物细胞工厂进行天然产物的生物生产是替代传统植物提取的一种很有前途的方法。最近，非传统微生物已成为生物制造有吸引力的底盘宿主。一种这样的微生物，即多形被孢霉是一种用于蛋白质表达的工业酵母，具有许多优点，如耐热性、广泛的底物谱和高密度发酵。在这里，我们通过优化甲羟戊酸途径、增强 NADPH 和乙酰辅酶 A 的供应以及下调竞争途径，系统地重新布线了 O. polymorpha 的细胞代谢，以实现倍半萜烯 β-榄香烯的高水平生产。工程菌株在分批和补料分批发酵中分别产生了 509mg/L 和 4.7g/L 的 β-榄香烯。因此，本研究确定了 O. polymorpha 作为生产倍半萜烯的良好微生物平台的潜在工业应用。
