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硫解酶超家族:具有多种反应特异性的缩合酶

The thiolase superfamily: condensing enzymes with diverse reaction specificities.

作者信息

Haapalainen Antti M, Meriläinen Gitte, Wierenga Rik K

机构信息

Biocenter Oulu and Department of Biochemistry, University of Oulu, PO Box 3000, FIN-90014, Finland.

出版信息

Trends Biochem Sci. 2006 Jan;31(1):64-71. doi: 10.1016/j.tibs.2005.11.011. Epub 2005 Dec 13.

DOI:10.1016/j.tibs.2005.11.011
PMID:16356722
Abstract

The formation of a carbon-carbon bond is an essential step in the biosynthetic pathways by which fatty acids and polyketides are made. The thiolase superfamily enzymes catalyse this carbon-carbon-bond formation via a thioester-dependent Claisen-condensation-reaction mechanism. In this way, fatty-acid chains and polyketides are made by sequentially adding simple building blocks, such as acetate units, to the growing molecule. A common feature of these enzymes is a reactive cysteine residue that is transiently acylated in the catalytic cycle. The wide catalytic diversity of the thiolase superfamily enzymes is of great interest. In particular, the type-III polyketide synthases make complicated compounds of great biological importance using multiple, subsequent condensation reactions, which are all catalysed in the same active-site cavity. The crucial metabolic importance of the bacterial fatty-acid-synthesizing enzymes stimulates in-depth studies that aim to develop efficient anti-bacterial drugs.

摘要

碳-碳键的形成是脂肪酸和聚酮化合物生物合成途径中的关键步骤。硫解酶超家族的酶通过硫酯依赖性克莱森缩合反应机制催化这种碳-碳键的形成。通过这种方式,脂肪酸链和聚酮化合物是通过将简单的构建单元(如乙酸酯单元)依次添加到生长的分子中形成的。这些酶的一个共同特征是一个反应性半胱氨酸残基,它在催化循环中会短暂地被酰化。硫解酶超家族酶广泛的催化多样性备受关注。特别是,III型聚酮化合物合酶利用多个后续缩合反应生成具有重要生物学意义的复杂化合物,所有这些反应都在同一个活性位点腔内催化。细菌脂肪酸合成酶至关重要的代谢意义激发了旨在开发高效抗菌药物的深入研究。

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