Functional analysis of the MbtH-like protein superfamily

描述(由申请人提供)： 项目摘要/摘要MbtH样蛋白(MLP)超家族由相对较小的蛋白质(60-80个氨基酸)组成，仅在真核细菌中发现，最常见的与非核糖体多肽合成酶(NRP)相关。这个超家族是以其创始成员MbtH命名的，MbtH是结核分枝杆菌中Mycobactin生物合成途径中一个功能未知的蛋白质。这些蛋白与NRPS系统的共同联系表明，它们在非核糖体多肽的产生中发挥了一定的作用，但普遍的观点是，这些蛋白不参与NRPS的酶学。我们最近的数据表明，这一观点需要修正，因为我们已经表明，MLP影响异源过度生产的NRPS的溶解度和功能。我们的总体目标是了解MPLS如何影响NRPS酶学，以及MLP和NRPS如何在分子水平上发生相互作用，以提供一般功能和蛋白质-蛋白质相互作用的特异性。该项目的结果将对NRPS酶学的基本理解、利用代谢工程产生新的非核糖体肽衍生物、针对这些酶进行药物开发以及了解这些蛋白质在细菌生理学中的作用产生广泛的影响。

DESCRIPTION (provided by applicant): PROJECT SUMMARY/ABSTRACT The MbtH-like protein (MLP) superfamily consists of relatively small proteins (60-80 amino acids) that are found only in eubacteria and are most commonly associated with nonribosomal peptide synthetases (NRPS). This superfamily is named after its founding member MbtH, which is a protein of unknown function in the mycobactin biosynthesis pathway in Mycobacterium tuberculosis. The common association of these proteins with NRPS systems suggested that they play some role in nonribosomal peptide production, but the prevailing view was that these proteins were not involved in the enzymology of NRPSs. Our recent data suggest this view needs to be revised since we have shown MLPs impact the solubility and function of heterologously overproduced NRPSs. Our overall goal is to understand how MPLs influence NRPS enzymology and how the MLP and NRPS interactions occur at the molecular level to provide general function and protein-protein interaction specificity. The results from this project will have a broad impact on the basic understanding of NRPS enzymology, the generation of new derivatives of nonribosomal peptides using metabolic engineering, the targeting of these enzymes for drug development, and the understanding of the role these proteins have on bacterial physiology.