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微生物所高书山研究组在Natural Product Reports发表非铁血红素酶长篇综述

   微生物来源的天然产物和其相关的生物合成酶元件是新药发现与合成生物学研究的巨大资源宝库。在微生物体内众多的酶中,非血红素铁酶(non-haem iron enzyme)是一类含有血红素形态以外铁离子的多功能催化剂。它们广泛分布于生物体内的初级和次级代谢途径中,可以催化卤代反应、各种类型的氧化反应以及多种类型的重排反应,在天然产物生物合成和初级代谢产物的合成与降解过程中扮演着重要角色。
     高书山研究组与合作者们近日在天然产物(药物)化学权威期刊Natural Product Reports上发表综述,系统地总结了非血红素铁酶在生物合成过程中所催化的生物化学反应,描述了相关的生物合成途径,并阐述了相关的酶学机制,重点从结构生物学角度阐述了酶与底物之间的相互作用关系。
     高书山研究员为本文的第一作者,我所为第一单位;美国波士顿大学的刘平华教授和华东理工大学的刘学庭教授为通讯作者。 


Recent examples of α-ketoglutarate-dependent mononuclear non-haem iron enzymes in natural product biosyntheses

Shu-Shan Gao,  Nathchar Naowarojna,  Ronghai Cheng,  Xueting Liu*  and  Pinghua Liu* 

Abstract


α-Ketoglutarate (αKG, also known as 2-oxoglutarate)-dependent mononuclear non-haem iron (αKG-NHFe) enzymes catalyze a wide range of biochemical reactions, including hydroxylation, ring fragmentation, C–C bond cleavage, epimerization, desaturation, endoperoxidation and heterocycle formation. These enzymes utilize iron(II) as the metallo-cofactor and αKG as the co-substrate. Herein, we summarize several novel αKG-NHFe enzymes involved in natural product biosyntheses discovered in recent years, including halogenation reactions, amino acid modifications and tailoring reactions in the biosynthesis of terpenes, lipids, fatty acids and phosphonates. We also conducted a survey of the currently available structures of αKG-NHFe enzymes, in which αKG binds to the metallo-centre bidentately through either a proximal- or distal-type binding mode. Future structure–function and structure–reactivity relationship investigations will provide crucial information regarding how activities in this large class of enzymes have been fine-tuned in nature.

        文章链接: http://pubs.rsc.org/en/content/articlelanding/2018/np/c7np00067g 

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