Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems.
Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems.
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DOI：
10.3762/bjoc.13.85
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发表时间：
2017
影响因子：
2.7
通讯作者：
Brück T
中科院分区：
文献类型：
--
作者：
Kemper K;Hirte M;Reinbold M;Fuchs M;Brück T
萜类化合物有超过50，000种，是天然产物中最大和结构最多样化的一组。它们普遍存在于细菌、植物、动物和真菌中，具有多种生物学功能，如细胞壁成分或防御机制。工业应用包括药品、食品添加剂、维生素、香料、燃料和燃料添加剂等。所有萜烯的中心结构单元是类异戊二烯化合物异戊烯基二磷酸和二甲基烯丙基二磷酸。像大肠杆菌这样的细菌具有这些类异戊二烯的天然代谢途径，这对于基因工程来说是非常适合的。与重组萜烯生物合成模块一起，它们是用于高价值萜烯的异源生产的非常合适的宿主。然而，与提取和表征的萜烯的数量相反，对特别是参与高度官能化化合物形成的特定生物合成酶知之甚少。在这篇评论中讨论的新方法包括代谢工程以及定点诱变，以扩大天然萜烯景观。主要集中在工程生物合成途径的成功整合到优化的萜烯生产大肠杆菌的验证，这篇综述将提供一个洞察力，在最近的进展，主要是二萜脱氢酶的操作。
With over 50.000 identified compounds terpenes are the largest and most structurally diverse group of natural products. They are ubiquitous in bacteria, plants, animals and fungi, conducting several biological functions such as cell wall components or defense mechanisms. Industrial applications entail among others pharmaceuticals, food additives, vitamins, fragrances, fuels and fuel additives. Central building blocks of all terpenes are the isoprenoid compounds isopentenyl diphosphate and dimethylallyl diphosphate. Bacteria like Escherichia coli harbor a native metabolic pathway for these isoprenoids that is quite amenable for genetic engineering. Together with recombinant terpene biosynthesis modules, they are very suitable hosts for heterologous production of high value terpenes. Yet, in contrast to the number of extracted and characterized terpenes, little is known about the specific biosynthetic enzymes that are involved especially in the formation of highly functionalized compounds. Novel approaches discussed in this review include metabolic engineering as well as site-directed mutagenesis to expand the natural terpene landscape. Focusing mainly on the validation of successful integration of engineered biosynthetic pathways into optimized terpene producing Escherichia coli, this review shall give an insight in recent progresses regarding manipulation of mostly diterpene synthases.