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聚酮合酶基因操作:工程化新型抗生素的结构-功能方法

Polyketide synthase gene manipulation: a structure-function approach in engineering novel antibiotics.

作者信息

Hutchinson C R, Fujii I

机构信息

School of Pharmacy, University of Wisconsin, Madison 53706, USA.

出版信息

Annu Rev Microbiol. 1995;49:201-38. doi: 10.1146/annurev.mi.49.100195.001221.

DOI:10.1146/annurev.mi.49.100195.001221
PMID:8561459
Abstract

Polyketides are produced primarily in microorganisms through a specialized metabolism that is a variation of fatty acid biosynthesis. A strong sequence and mechanistic similarity among many of the fatty acid and polyketide synthase enzymes has led to two paradigms for explaining polyketide biochemistry. In one, polyketides are formed by enzyme complexes consisting of four to seven monofunctional proteins in which the beta-carbonyl groups of the intermediates resulting from the condensation of acetate residues are largely not reduced and cyclization of the intermediates typically produces aromatic compounds. The intermediates in the other model are formed by multifunctional enzymes in which each of the initial condensation products is processed through reduction; reduction and dehydration; or reduction, dehydration, and further reduction cycles to produce highly reduced compounds from acetate, propionate, and butyrate residues. Expression of the genes encoding each type of polyketide synthase, or their mutant forms, has provided much information about the underlying biochemistry and, in some cases, resulted in the formation of novel natural products.

摘要

聚酮化合物主要在微生物中通过一种特殊的代谢过程产生,这种代谢过程是脂肪酸生物合成的一种变体。许多脂肪酸和聚酮合酶之间存在很强的序列和机制相似性,这导致了两种解释聚酮生物化学的范例。在一种范例中,聚酮化合物由由四到七个单功能蛋白质组成的酶复合物形成,其中乙酸盐残基缩合产生的中间体的β-羰基基团在很大程度上未被还原,中间体的环化通常产生芳香族化合物。另一种模型中的中间体由多功能酶形成,其中每个初始缩合产物都经过还原;还原和脱水;或还原、脱水和进一步的还原循环,以从乙酸盐、丙酸盐和丁酸盐残基产生高度还原的化合物。编码每种类型聚酮合酶或其突变形式的基因的表达提供了许多关于潜在生物化学的信息,并且在某些情况下,导致了新型天然产物的形成。

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