Duan Yali, Liu Jiawei, Du Yun, Pei Xiaolin, Li Mu
Hubei International Scientific and Technological Cooperation Base of Traditional Fermented Foods, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
Key Laboratory of Environment Correlative Dietology, Ministry of Education, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
J Agric Food Chem. 2021 Mar 3;69(8):2501-2511. doi: 10.1021/acs.jafc.0c06563. Epub 2021 Feb 18.
The iridoids and their derivatives monoterpene indole alkaloids (MIAs) are two broad classes of plant-derived natural products with valuable pharmaceutical properties. However, the poor source limited their application. Nepetalactol, a common iridoid scaffold of MIAs, was heterologously produced in . Although the optimization of nepetalactol production in was achieved by metabolic engineering, the inherent metabolic constraints impose a restriction on the production. Herein, we developed a high nepetalactol-producing platform strain. First, the co-expression of 5 nepetalactol biosynthetic genes, in a high isopentenyl pyrophosphate (IPP)-producing strain AK2, succeeded in the biosynthesis of nepetalactol. Second, the improvement of the IPP supply and the suppression of the byproduct citronellol formation were simultaneously achieved. Finally, the highest titer of nepetalactol of 7.2 mg/L was obtained with the engineered strain, after the optimization of the carbon source. To the best of our knowledge, this is the highest reported titer of nepetalactol in microbial cells. The developed strain represents an attractive biosynthetic platform host for the production of iridoids and MIAs.
环烯醚萜及其衍生物单萜吲哚生物碱（MIAs）是两类具有重要药用特性的植物源天然产物。然而，其来源有限限制了它们的应用。荆芥内酯是MIAs常见的环烯醚萜骨架，已在……中实现了异源生产。尽管通过代谢工程实现了……中荆芥内酯产量的优化，但内在的代谢限制对产量仍有制约。在此，我们构建了一个高产荆芥内酯的……平台菌株。首先，在高产异戊烯基焦磷酸（IPP）的菌株……AK2中共表达5个荆芥内酯生物合成基因，成功实现了荆芥内酯的生物合成。其次，同时实现了IPP供应的改善和副产物香茅醇形成的抑制。最后，经过碳源优化，工程菌株获得了最高7.2 mg/L的荆芥内酯产量。据我们所知，这是微生物细胞中报道的荆芥内酯的最高产量。所构建的……菌株是用于环烯醚萜和MIAs生产的有吸引力的生物合成平台宿主。
