Construction and Optimization of Nonclassical Isoprenoid Biosynthetic Pathways in Yeast Peroxisomes for (+)-Valencene Production
Construction and Optimization of Nonclassical Isoprenoid Biosynthetic Pathways in Yeast Peroxisomes for (+)-Valencene Production
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DOI：
10.1021/acs.jafc.3c02932
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发表时间：
2023-07-12
影响因子：
6.1
通讯作者：
Zhou, Yongjin J.
中科院分区：
文献类型：
--
作者：
Cao, Chunyang;Zhang, Haiyan;Zhou, Yongjin J.
类异戊二烯是一种具有多种生物活性的天然产物，但其植物提取物的浓度较低。合成生物学的迅速发展为利用工程微生物生产高附加值天然产物提供了一条可持续发展的途径。然而，细胞代谢的复杂性使得具有代谢相互作用的内源性类异戊二烯生物合成途径的工程化变得困难。在此，我们首次构建并优化了酵母过氧化物酶体合成倍半萜（+）-朱栾倍半萜的三种类异戊二烯途径（盐古菌型、热原体型和类异戊二烯醇途径）。在酵母中，盐古菌型MVA途径比经典MVA途径更有效。MVK和IPK是盐古菌MVA途径的限速步骤，摇瓶补料分批发酵可生产869 mg/L（+）-朱栾倍半萜。本工作拓展了类异戊二烯在真核生物中的合成途径，为类异戊二烯的合成提供了一条更有效的途径。
Isoprenoids are a kind of natural product with variousactivities,but their plant extraction suffers low concentration. The rapid developmentof synthetic biology offers a sustainable route for supply of high-value-addednatural products by engineering microorganisms. However, the complexityof cellular metabolism makes engineering endogenous isoprenoid biosyntheticpathways with metabolic interaction difficult. Here, for the firsttime, we constructed and optimized three types of isoprenoid pathways(the Haloarchaea-type, Thermoplasma-type, and isoprenoid alcohol pathway) in yeast peroxisomes for thesynthesis of sesquiterpene (+)-valencene. In yeast, the Haloarchaea-type MVA pathway is more effective than the classical MVA pathway. MVK and IPK were determined to be the rate-limitingsteps of the Haloarchaea-type MVA pathway, and theproduction of 869 mg/L (+)-valencene under fed-batch fermentationin shake flasks was realized. This work expands isoprenoid synthesisin eukaryotes and provides a more efficient pathway for isoprenoidsynthesis.