Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis.
Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis.
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DOI：
10.1002/anie.201510650
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发表时间：
2016-02-05
期刊：
影响因子：
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通讯作者：
Hamberger B
中科院分区：
文献类型：
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作者：
Andersen-Ranberg J;Kongstad KT;Nielsen MT;Jensen NB;Pateraki I;Bach SS;Hamberger B;Zerbe P;Staerk D;Bohlmann J;Møller BL;Hamberger B
植物源性二萜类化合物是重要的药物、食品添加剂和香料，但其天然丰度低和结构复杂性高限制了其更广泛的工业应用。通过模拟植物中二萜生物合成的模块性，我们构建了51种I类和II类二萜脱氢酶的功能组合，其中41种是“新的”。 立体选择性生物合成超过50个二萜骨架，包括天然变体和新的对映体或非对映体的对应物。在酿酒酵母工程菌株中完成了四个工业相关目标的可扩展生物技术生产。
Plant‐derived diterpenoids serve as important pharmaceuticals, food additives, and fragrances, yet their low natural abundance and high structural complexity limits their broader industrial utilization. By mimicking the modularity of diterpene biosynthesis in plants, we constructed 51 functional combinations of class I and II diterpene synthases, 41 of which are “new‐to‐nature”. Stereoselective biosynthesis of over 50 diterpene skeletons was demonstrated, including natural variants and novel enantiomeric or diastereomeric counterparts. Scalable biotechnological production for four industrially relevant targets was accomplished in engineered strains of Saccharomyces cerevisiae.