Diversity of P450 enzymes in the biosynthesis of natural products.

Diversity of P450 enzymes in the biosynthesis of natural products.
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DOI:
10.1039/c2np20020a
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发表时间:
2012-10
影响因子:
11.9
通讯作者:
Sherman DH
Sherman DH
中科院分区:
化学1区
文献类型:
--
作者:
Podust LM;Sherman DH

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在微生物和植物中,通过次级代谢途径产生的天然产物的多样性氧化模式主要通过细胞色素P450酶(P450 s)催化的剪裁反应来实现。P450是氧化血红素蛋白的一个大家族,存在于从原核生物到人类的所有生命形式中。了解这些迷人的C-H键活化催化剂的反应性和选择性将促进它们在生产有价值的药物和医药,农业和工业产品中的应用。这个P450组的一个主要优势是它建立的酶-底物关系,P450酶如何工作的最详细的知识的来源。工程微生物衍生的P450酶,以适应替代底物和添加新的功能仍然是一个重要的近期和长期的实际目标,推动这些分子的结构表征。了解P450结构-功能的自然进化应加速代谢工程和定向进化方法,以增强天然产物结构和其他生物合成应用的多样化。
Diverse oxygenation patterns of natural products generated by secondary metabolic pathways in microorganisms and plants are largely achieved through the tailoring reactions catalysed by cytochrome P450 enzymes (P450s). P450s are a large family of oxidative hemoproteins found in all life forms from prokaryotes to humans. Understanding the reactivity and selectivity of these fascinating C-H bond-activating catalysts will advance their use in generating valuable pharmaceuticals and products for medicine, agriculture and industry. A major strength of this P450 group is its set of established enzyme-substrate relationships, the source of the most detailed knowledge on how P450 enzymes work. Engineering microbial-derived P450 enzymes to accommodate alternative substrates and add new functions continues to be an important near- and long-term practical goal driving the structural characterization of these molecules. Understanding the natural evolution of P450 structure-function should accelerate metabolic engineering and directed evolutionary approaches to enhance diversification of natural product structures and other biosynthetic applications.
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