NRPS-PKS: a knowledge-based resource for analysis of NRPS/PKS megasynthases
NRPS-PKS: a knowledge-based resource for analysis of NRPS/PKS megasynthases
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DOI：
10.1093/nar/gkh359
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发表时间：
2004-07-01
影响因子：
14.9
通讯作者：
Mohanty, D
中科院分区：
文献类型：
--
作者：
Ansari, MZ;Yadav, G;Mohanty, D
NRPS-PKS是一种基于网络的软件，用于分析与环孢素、利福霉素和红霉素等具有重要药用价值的天然产物的生物合成有关的大型多酶、多结构域巨合酶。NRPS-PKS是在对几个实验表征的生物合成基因簇的序列和结构特征进行综合分析的基础上开发出来的。这些分析的结果被组织成四个综合的可搜索数据库，用于阐明非核糖体肽合成酶和三种类型的聚酮合成酶的结构域组织和底物专一性。这些数据库作为NRPS-PKS的后端，为预测未表征的NRPS/PKS簇的结构域组织和底物特异性提供了知识库。在一大组生物合成基因簇上的基准测试表明，除了正确识别NRPS和PKS结构域外，NRPS-PKS还可以相当高的精度预测腺化和酰基转移酶结构域的特异性。NRPS-PKS的这些特征使其成为鉴定新测序基因组中发现的NRPS/PKS基因簇生物合成的天然产物的宝贵资源。NRPS-PKS中包含的基因簇的训练和测试集关联了307个开放阅读框、2223个功能蛋白结构域、68个起始/延伸前体及其特定识别基序的信息，以及来自四个不同家族的101个天然产物的化学结构。NRPS-PKS是一个独特的资源，它提供了一个用户友好的界面，用于将天然产物的化学结构与相应的非核糖体多肽合成酶或聚酮合成酶中的结构域和模块关联起来。它还提供了结构域/模块交换以及定点突变实验的指南，以设计新的天然产品的生物合成。NRPS-PKS可在http://www.nii.res.in/nrps-pks.html.上访问
NRPS-PKS is web-based software for analysing large multi-enzymatic, multi-domain megasynthases that are involved in the biosynthesis of pharmaceutically important natural products such as cyclosporin, rifamycin and erythromycin. NRPS-PKS has been developed based on a comprehensive analysis of the sequence and structural features of several experimentally characterized biosynthetic gene clusters. The results of these analyses have been organized as four integrated searchable databases for elucidating domain organization and substrate specificity of nonribosomal peptide synthetases and three types of polyketide synthases. These databases work as the backend of NRPS-PKS and provide the knowledge base for predicting domain organization and substrate specificity of uncharacterized NRPS/PKS clusters. Benchmarking on a large set of biosynthetic gene clusters has demonstrated that, apart from correct identification of NRPS and PKS domains, NRPS-PKS can also predict specificities of adenylation and acyltransferase domains with reasonably high accuracy. These features of NRPS-PKS make it a valuable resource for identification of natural products biosynthesized by NRPS/PKS gene clusters found in newly sequenced genomes. The training and test sets of gene clusters included in NRPS-PKS correlate information on 307 open reading frames, 2223 functional protein domains, 68 starter/extender precursors and their specific recognition motifs, and also the chemical structure of 101 natural products from four different families. NRPS-PKS is a unique resource which provides a user-friendly interface for correlating chemical structures of natural products with the domains and modules in the corresponding nonribosomal peptide synthetases or polyketide synthases. It also provides guidelines for domain/module swapping as well as site-directed mutagenesis experiments to engineer biosynthesis of novel natural products. NRPS-PKS can be accessed at http://www.nii.res.in/nrps-pks.html.