Singh Mangal, Chaudhary Sandeep, Sareen Dipti
Department of Biochemistry, Panjab University, Chandigarh, India.
J Biosci. 2017 Mar;42(1):175-187. doi: 10.1007/s12038-017-9663-z.
Non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) present in bacteria and fungi are the major multi-modular enzyme complexes which synthesize secondary metabolites like the pharmacologically important antibiotics and siderophores. Each of the multiple modules of an NRPS activates a different amino or aryl acid, followed by their condensation to synthesize a linear or cyclic natural product. The studies on NRPS domains, the knowledge of their gene cluster architecture and tailoring enzymes have helped in the in silico genetic screening of the ever-expanding sequenced microbial genomic data for the identification of novel NRPS/PKS clusters and thus deciphering novel non-ribosomal peptides (NRPs). Adenylation domain is an integral part of the NRPSs and is the substrate selecting unit for the final assembled NRP. In some cases, it also requires a small protein, the MbtH homolog, for its optimum activity. The presence of putative adenylation domain and MbtH homologs in a sequenced genome can help identify the novel secondary metabolite producers. The role of the adenylation domain in the NRPS gene clusters and its characterization as a tool for the discovery of novel cryptic NRPS gene clusters are discussed.
细菌和真菌中存在的非核糖体肽合成酶（NRPSs）和聚酮化合物合成酶（PKSs）是主要的多模块酶复合物，它们合成次生代谢产物，如具有重要药理作用的抗生素和铁载体。NRPS的多个模块中的每一个都激活一种不同的氨基酸或芳基酸，然后将它们缩合以合成线性或环状天然产物。对NRPS结构域的研究、对其基因簇结构和修饰酶的了解，有助于对不断扩展的已测序微生物基因组数据进行计算机遗传筛选，以鉴定新的NRPS/PKS簇，从而破译新的非核糖体肽（NRPs）。腺苷化结构域是NRPSs的一个组成部分，是最终组装的NRP的底物选择单元。在某些情况下，它还需要一种小蛋白，即MbtH同源物，以实现其最佳活性。在已测序的基因组中存在推定的腺苷化结构域和MbtH同源物有助于鉴定新的次生代谢产物生产者。本文讨论了腺苷化结构域在NRPS基因簇中的作用及其作为发现新的隐秘NRPS基因簇工具的特征。
