天然产物巨合酶中 docking 结构域介导的亚基相互作用。

Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.

Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.

J Ind Microbiol Biotechnol. 2021 Jun 4;48(3-4). doi: 10.1093/jimb/kuab018.

Polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) multienzymes produce numerous high value metabolites. The protein subunits which constitute these megasynth(et)ases must undergo ordered self-assembly to ensure correct organisation of catalytic domains for the biosynthesis of a given natural product. Short amino acid regions at the N- and C-termini of each subunit, termed docking domains (DDs), often occur in complementary pairs, which interact to facilitate substrate transfer and maintain pathway fidelity. This review details all structurally characterised examples of NRPS and PKS DDs to date and summarises efforts to utilise DDs for the engineering of biosynthetic pathways.

聚酮合酶（PKS）和非核糖体肽合酶（NRPS）多酶产生许多高价值代谢物。构成这些巨合酶的蛋白质亚基必须经历有序的自组装，以确保正确组织催化结构域以合成给定的天然产物。每个亚基的 N-和 C-末端的短氨基酸区域，称为对接结构域（DD），通常以互补对的形式出现，相互作用以促进底物转移并保持途径保真度。这篇综述详细介绍了迄今为止所有结构特征明确的 NRPS 和 PKS DD 实例，并总结了利用 DD 工程生物合成途径的努力。