Evaluation of Biosynthetic Pathway and Engineered Biosynthesis of Alkaloids.
Evaluation of Biosynthetic Pathway and Engineered Biosynthesis of Alkaloids.
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DOI：
10.3390/molecules21081078
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发表时间：
2016-08-18
期刊：
影响因子：
--
通讯作者：
Watanabe K
中科院分区：
文献类型：
--
作者：
Kishimoto S;Sato M;Tsunematsu Y;Watanabe K
已知各种生物体（包括细菌、真菌和植物）产生多种生物碱，作为表现出有用的生物活性的次级代谢产物。然而，对这些代谢物如何生物合成的理解仍然有限，因为这些化合物中的大多数是从植物中分离出来的，并且处于微量生产水平。在这篇综述中，我们集中在最近的努力，确定负责这些含氮天然产物的生物合成的基因，并阐明在生物合成过程中所涉及的机制。在这篇评论中讨论的生物碱是ditryptophenaline（二聚二酮哌嗪生物碱），saframycin（四氢异喹啉生物碱），strictosidine（单萜吲哚生物碱），麦角胺（麦角生物碱）和阿片类药物（苄基异喹啉和吗啡烷生物碱）。本文还讨论了这些化合物的工程生物合成，主要是通过异源重建的目标生物合成途径在合适的主机，如大肠杆菌，酿酒酵母和构巢曲霉。这些异源生物合成系统可用于确认分离基因的功能，经济地扩大商业分布的生物碱生产，并设计生物合成途径以生产有价值的生物碱类似物。特别是，广泛参与氧化还原酶，如细胞色素P450催化的氧化反应，在次生代谢产物的生物合成进行了详细讨论。
Varieties of alkaloids are known to be produced by various organisms, including bacteria, fungi and plants, as secondary metabolites that exhibit useful bioactivities. However, understanding of how those metabolites are biosynthesized still remains limited, because most of these compounds are isolated from plants and at a trace level of production. In this review, we focus on recent efforts in identifying the genes responsible for the biosynthesis of those nitrogen-containing natural products and elucidating the mechanisms involved in the biosynthetic processes. The alkaloids discussed in this review are ditryptophenaline (dimeric diketopiperazine alkaloid), saframycin (tetrahydroisoquinoline alkaloid), strictosidine (monoterpene indole alkaloid), ergotamine (ergot alkaloid) and opiates (benzylisoquinoline and morphinan alkaloid). This review also discusses the engineered biosynthesis of these compounds, primarily through heterologous reconstitution of target biosynthetic pathways in suitable hosts, such as Escherichia coli, Saccharomyces cerevisiae and Aspergillus nidulans. Those heterologous biosynthetic systems can be used to confirm the functions of the isolated genes, economically scale up the production of the alkaloids for commercial distributions and engineer the biosynthetic pathways to produce valuable analogs of the alkaloids. In particular, extensive involvement of oxidation reactions catalyzed by oxidoreductases, such as cytochrome P450s, during the secondary metabolite biosynthesis is discussed in details.
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影响因子：
4.9
作者：
ARAI, T;YAZAWA, K;MIKAMI, Y
通讯作者：
MIKAMI, Y
影响因子：
3.6
作者：
BARROW, CJ;CAI, P;COOPER, R
通讯作者：
COOPER, R
影响因子：
15
作者：
GEBLER, JC;WOODSIDE, AB;POULTER, CD
通讯作者：
POULTER, CD
影响因子：
4.3
作者：
Gesell, Andreas;Diaz Chavez, Maria Luisa;Kutchan, Toni M.
通讯作者：
Kutchan, Toni M.
多司他嗪和多司他酰胺是植物病原真菌多盘拟盘菌的生物活性代谢物
影响因子：
5.1
作者：
Ding, Gang;Jiang, Lihua;Che, Yongsheng
通讯作者：
Che, Yongsheng