单萜吲哚生物碱的合成生物学研究进展
收稿日期: 2018-06-01
修回日期: 2018-08-04
网络出版日期: 2018-08-14
基金资助
上海市科学技术委员会（Nos.18ZR1447000，15JC1400402）资助项目.
Synthetic Biology Studies of Monoterpene Indole Alkaloids
Received date: 2018-06-01
Revised date: 2018-08-04
Online published: 2018-08-14
Supported by
Project supported by the Science and Technology Commission of Shanghai Municipality (Nos. 18ZR1447000, 15JC1400402).
单萜吲哚生物碱是一类具有重要药用价值的天然产物，但是在其宿主的生物含量很低；虽然通过有机化学的方法可以实现该类复杂结构化合物的全合成，但是难以大量快速获得，而且围绕核心骨架的进一步衍生化修饰也有一定的瓶颈.随着单萜吲哚生物碱生物合成途径的解析和合成生物学使能技术的发展，利用合成生物学策略结合化学半合成将是实现该类化合物的合成制造和通量结构衍生化的重要发展趋势.单萜吲哚生物碱基因元件的挖掘鉴定和生物合成途径的解析是进行合成生物学研究的前提条件.异胡豆苷是单萜吲哚生物碱合成的关键骨架化合物，由色胺和开环马钱子苷汇聚合成，这一过程被称为上游合成途径；以异胡豆苷为骨架形成各种单萜吲哚生物碱的过程称为下游合成途径.从这两个方面对近30年来单萜吲哚生物碱合成元件的发现和合成生物学研究进展进行了综述，为后续合成生物学的应用研究奠定基础.
吴世文 , 杨盟权 , 肖友利 . 单萜吲哚生物碱的合成生物学研究进展[J]. 有机化学, 2018 , 38(9) : 2243 -2258 . DOI: 10.6023/cjoc201806001
Monoterpene indole alkaloids (MIAs) are a group of important specialized metabolites that exhibit a broad range of pharmacological activities. However, the contents of MIAs in natural plants are extremely low. It could be produced through advanced synthetic chemistry, but the production scale is very limited, and the further modification of the key scaffold is very difficult. With the full elucidation of MIAs biosynthetic pathway and deeper investigation of biotechnology in synthetic biology, the use of synthetic biology strategies combined with chemical semi-synthesis will be an important development trend for the synthesis of these compounds and their derivatives. Elucidation of MIAs biosynthetic pathway by characterizing involved genes is the prerequisite for synthetic biology. Strictosidine, which was formed by the combination of tryptamine and secologanin, is the key intermediate for MIAs biosynthesis. The discovery of biological parts and research advances of synthetic biology of MIAs based on the upstream biosynthetic pathway, the formation of strictosidine, and downstream biosynthetic pathway, production of divergent MIAs derived from strictosidine over the past three decades are described. This review could provide guidance for further elucidation of other MIAs and promotion of synthetic biology for producing MIAs.
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