Biosynthesis of phosphonic and phosphinic acid natural products.

Biosynthesis of phosphonic and phosphinic acid natural products.
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DOI:
10.1146/annurev.biochem.78.091707.100215
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发表时间:
2009
影响因子:
16.6
通讯作者:
van der Donk WA
van der Donk WA
中科院分区:
生物学1区
文献类型:
--
作者:
Metcalf WW;van der Donk WA

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含有碳-磷键的天然产物(膦酸和次膦酸)已广泛用于医学和农业。近年来,随着几个家族成员的生物合成基因簇的克隆,这些化合物的生物化学和生物学重新引起了人们的兴趣。这篇综述讨论了这些化合物生物合成背后的分子逻辑的共性和差异。目前的知识有关的代谢途径和酶参与生产的一些天然产物,包括批准的抗生素磷霉素,广泛使用的除草剂膦丝菌素,和临床候选人治疗疟疾FR 900098,提出。参与这些化合物生物合成的许多酶催化化学和生物学上前所未有的转化,并且通过它们的研究揭示了丰富的新生物化学。这些研究也为天然产物的发现提出了新的策略。
Natural products containing carbon-phosphorus bonds (phosphonic and phosphinic acids) have found widespread use in medicine and agriculture. Recent years have seen a renewed interest in the biochemistry and biology of these compounds with the cloning of the biosynthetic gene clusters for several family members. This review discusses the commonalities and differences in the molecular logic that lies behind the biosynthesis of these compounds. The current knowledge regarding the metabolic pathways and enzymes involved in the production of a number of natural products, including the approved antibiotic fosfomycin, the widely used herbicide phosphinothricin, and the clinical candidate for treatment of malaria FR900098, is presented. Many of the enzymes involved in the biosynthesis of these compounds catalyze chemically and biologically unprecedented transformations and a wealth of new biochemistry has been revealed through their study. These studies have also suggested new strategies for natural product discovery.
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