Protein-protein interface analysis of the non-ribosomal peptide synthetase peptidyl carrier protein and enzymatic domains.
Protein-protein interface analysis of the non-ribosomal peptide synthetase peptidyl carrier protein and enzymatic domains.
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DOI：
10.1016/j.synbio.2022.02.006
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发表时间：
2022-06
影响因子：
4.8
通讯作者：
Burkart MD
中科院分区：
文献类型：
--
作者：
Corpuz JC;Sanlley JO;Burkart MD
非核糖体肽合成酶（NRPS）由于其模块化结构及其产物的治疗相关性而成为生物合成途径工程的有吸引力的靶标。通过肽基载体蛋白（PCP）及其伴侣酶之间形成的特异性蛋白质-蛋白质相互作用介导的催化作用，NRPS酶学和控制仍然是发现的肥沃土壤。本文综述了近年来在结构生物学方面的研究进展，包括高分辨率结构数据的整理，揭示了PCP与其伴侣酶之间形成的各种蛋白质-蛋白质界面，包括磷酸泛酰巯基乙胺基转移酶（PPTase）、腺苷酸化（A）结构域、缩合（C）结构域、硫酯酶（TE）结构域和合成酶中的其他剪裁酶。将我们对PCP如何识别伙伴蛋白的理解与使用定向进化和组合生物合成方法的潜力相结合，将增强未来发现和生产新生物活性化合物的努力。
Non-ribosomal peptide synthetases (NRPSs) are attractive targets for biosynthetic pathway engineering due to their modular architecture and the therapeutic relevance of their products. With catalysis mediated by specific protein-protein interactions formed between the peptidyl carrier protein (PCP) and its partner enzymes, NRPS enzymology and control remains fertile ground for discovery. This review focuses on the recent efforts within structural biology by compiling high-resolution structural data that shed light into the various protein-protein interfaces formed between the PCP and its partner enzymes, including the phosphopantetheinyl transferase (PPTase), adenylation (A) domain, condensation (C) domain, thioesterase (TE) domain and other tailoring enzymes within the synthetase. Integrating our understanding of how the PCP recognizes partner proteins with the potential to use directed evolution and combinatorial biosynthetic methods will enhance future efforts in discovery and production of new bioactive compounds.
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影响因子：
4.1
作者：
Corpuz JC;Podust LM;Davis TD;Jaremko MJ;Burkart MD
通讯作者：
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