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通过代谢工程提高香叶基香叶醇产量并利用异戊烯醇作为底物

Enhancing Geranylgeraniol Production by Metabolic Engineering and Utilization of Isoprenol as a Substrate in .

作者信息

Wang Junhua, Zhu Linghuan, Li Youran, Xu Sha, Jiang Wei, Liang Chaojuan, Fang Yakun, Chu Alex, Zhang Liang, Ding Zhongyang, Shi Guiyang

机构信息

Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, People's Republic of China.

National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, People's Republic of China.

出版信息

J Agric Food Chem. 2021 Apr 21;69(15):4480-4489. doi: 10.1021/acs.jafc.1c00508. Epub 2021 Apr 7.

DOI:10.1021/acs.jafc.1c00508
PMID:33823596
Abstract

The amount of geranylgeranyl diphosphate (GGPP) is vital for microbial production of geranylgeraniol (GGOH) in . In this study, a GGPP synthase with stronger catalytic ability was used to increase the supply of GGPP, and an engineered strain producing 374.02 mg/L GGOH at the shake flask level was constructed. Then, by increasing the metabolic flux of the mevalonate (MVA) pathway and the supply of isopentenyl pyrophosphate (IPP), the titer was further increased to 772.98 mg/L at the shake flask level, and we achieved the highest GGOH titer to date of 5.07 g/L in a 5 L bioreactor. This is the first report on the utilization of isoprenol for increasing the amount of IPP and enhancing GGOH production in . In the future, these strategies and engineered strains can be used to enhance the production of other terpenoids in .

摘要

香叶基香叶基二磷酸(GGPP)的量对于微生物生产香叶基香叶醇(GGOH)至关重要。在本研究中,使用了具有更强催化能力的GGPP合酶来增加GGPP的供应,并构建了在摇瓶水平下产生374.02 mg/L GGOH的工程菌株。然后,通过增加甲羟戊酸(MVA)途径的代谢通量和异戊烯基焦磷酸(IPP)的供应,在摇瓶水平下将滴度进一步提高到772.98 mg/L,并且在5 L生物反应器中我们实现了迄今为止最高的GGOH滴度5.07 g/L。这是关于利用异戊烯醇增加IPP量并提高GGOH产量的首次报道。未来,这些策略和工程菌株可用于提高其他萜类化合物的产量。

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