Biosynthetic pathways of ergot alkaloids.

Biosynthetic pathways of ergot alkaloids.
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DOI:
10.3390/toxins6123281
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发表时间:
2014-12-10
期刊:
影响因子:
4.2
通讯作者:
Li SM
Li SM
中科院分区:
医学2区
文献类型:
--
作者:
Gerhards N;Neubauer L;Tudzynski P;Li SM

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麦角生物碱是含氮天然产物,属于吲哚类生物碱。最著名的生产者是子囊菌门的真菌,如锁骨菌、Epichloë、青霉菌和曲霉菌。根据结构,麦角生物碱可分为三大类:麦角酸酰胺类、麦角酸酰胺类和肽类(麦角肽类)。它们都共享了形成四环麦角碱环系统的第一个生物合成步骤(除了最简单的三环化合物:chanoclavine)。通过特定的酶对麦角碱环进行不同的修饰,产生丰富的生物活性天然产物,这些产物可用作药物或其前体。从20世纪50年代到近年来,大多数生物合成途径已被阐明。来自几个麦角生物碱生产者的基因簇已经通过基因组挖掘确定,其中许多基因的功能已经通过敲除实验或对过量产生的酶的生化研究得到证实。
Ergot alkaloids are nitrogen-containing natural products belonging to indole alkaloids. The best known producers are fungi of the phylum Ascomycota, e.g., Claviceps, Epichloë, Penicillium and Aspergillus species. According to their structures, ergot alkaloids can be divided into three groups: clavines, lysergic acid amides and peptides (ergopeptines). All of them share the first biosynthetic steps, which lead to the formation of the tetracyclic ergoline ring system (except the simplest, tricyclic compound: chanoclavine). Different modifications on the ergoline ring by specific enzymes result in an abundance of bioactive natural products, which are used as pharmaceutical drugs or precursors thereof. From the 1950s through to recent years, most of the biosynthetic pathways have been elucidated. Gene clusters from several ergot alkaloid producers have been identified by genome mining and the functions of many of those genes have been demonstrated by knock-out experiments or biochemical investigations of the overproduced enzymes.
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