聚酮聚肽类天然产物生物合成过程中“多余”结构单元的引入、去除及其生物学意义

发布时间：2018-05-10 05:16

本文选题：聚酮聚肽 + “多余”结构单元　；参考：《科学通报》2017年31期

【摘要】：来源于动植物或微生物的天然产物,特别是聚酮类(polyketides,PKs)、非核糖体聚肽类(non-ribosomal peptides,NRPs)及其杂合化合物,由于其广泛而良好的生物活性而在现代医药产业中占有重要地位,引起人们极大的研究兴趣.近年来,在PKs,NRPs及其杂合类化合物的生物合成研究中,一些结构单元先被引入,再在后续反应中被去除的现象在某些分子中陆续被发现.这些结构单元包括脂肪酰基、氨基酸残基、非天然氨基酸残基和脂肪酰基-氨基酸等,其引入往往发生在聚酮合成酶或聚肽合成酶的装配线上,而去除发生在线下,并且去除机制差异巨大.更特别的是,这些结构单元看似多余,但实际上起到了非常重要的作用,例如作为生化反应的保护基团、控制后续生化反应指导分子组装、特殊的自身抗性保护机制等等.本文总结了2000年以来报道的这一类分子中额外结构单元的引入以及去除的生化过程,探讨这一过程在生命活动中的重要作用,从这些有限的例子中发现一些规律,为分析其他复杂生化反应和生物体生命活动提供线索,为其他化合物的生物合成途径研究提供参考,并且可以作为基因信息与化合物结构关联的重要桥梁为现代生物信息学分析提供依据.
[Abstract]:Natural products derived from plants, animals and microbes, especially polyketides (PKss), non-ribosomal peptides (NRPss) and their heterozygous compounds, play an important role in the modern pharmaceutical industry due to their broad and good biological activities. Arousing great interest in research. In recent years, in the biosynthesis of PKsNRPs and their heterozygous compounds, some structural units were first introduced and then removed from the subsequent reactions. These structural units include fatty acyl groups, amino acid residues, non-natural amino acid residues and aliphatic acyl-amino acids, which are introduced into the assembly line of polyketone synthetase or polypeptide synthetase and are removed from the assembly line. And the removal mechanism is very different. In particular, these structural units may seem superfluous, but they actually play a very important role, such as acting as protective groups for biochemical reactions, controlling subsequent biochemical reactions to direct molecular assembly, and special mechanisms for self-resistance protection, and so on. In this paper, the introduction and removal of extra structural units in this class of molecules reported since 2000 have been summarized, and the important role of this process in life activities has been discussed. Some laws have been found from these limited examples. Providing clues for the analysis of other complex biochemical reactions and biological activities, and providing references for the study of biosynthetic pathways of other compounds, It can be used as an important bridge between gene information and compound structure to provide basis for modern bioinformatics analysis.
【作者单位】：中国科学院上海有机化学研究所生命有机化学国家重点实验室;
【基金】：国家自然科学基金(21472231,31430005,21520102004,81302674) 上海市科学技术委员会重点项目(14JC1407700,15JC1400400) 中国科学院战略性先导科技专项(SQYZDJ-SSW-SLH1037,XDB20020200) K.C.Wong教育基金资助
【分类号】：O636

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