Khater Shradha, Anand Swadha, Mohanty Debasisa
Bioinformatics Center, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Synth Syst Biotechnol. 2016 Apr 1;1(2):80-88. doi: 10.1016/j.synbio.2016.03.001. eCollection 2016 Jun.
methods for linking genomic space to chemical space have played a crucial role in genomics driven discovery of new natural products as well as biosynthesis of altered natural products by engineering of biosynthetic pathways. Here we give an overview of available computational tools and then briefly describe a novel computational framework, namely retro-biosynthetic enumeration of biosynthetic reactions, which can add to the repertoire of computational tools available for connecting natural products to their biosynthetic gene clusters. Most of the currently available bioinformatics tools for analysis of secondary metabolite biosynthetic gene clusters utilize the "Genes to Metabolites" approach. In contrast to the "Genes to Metabolites" approach, the "Metabolites to Genes" or retro-biosynthetic approach would involve enumerating the various biochemical transformations or enzymatic reactions which would generate the given chemical moiety starting from a set of precursor molecules and identifying enzymatic domains which can potentially catalyze the enumerated biochemical transformations. In this article, we first give a brief overview of the presently available tools and approaches for analysis of secondary metabolite biosynthetic pathways. We also discuss our preliminary work on development of algorithms for retro-biosynthetic enumeration of biochemical transformations to formulate a novel computational method for identifying genes associated with biosynthesis of a given polyketide or nonribosomal peptide.
将基因组空间与化学空间相联系的方法在基于基因组学发现新天然产物以及通过生物合成途径工程改造来合成改造后的天然产物的过程中发挥了关键作用。在此，我们对现有的计算工具进行概述，然后简要描述一种新颖的计算框架，即生物合成反应的逆向生物合成枚举法，它可以丰富用于将天然产物与其生物合成基因簇相联系的计算工具种类。目前大多数用于分析次生代谢物生物合成基因簇的生物信息学工具都采用“基因到代谢物”的方法。与“基因到代谢物”方法不同，“代谢物到基因”或逆向生物合成方法将涉及枚举从一组前体分子开始生成给定化学部分的各种生化转化或酶促反应，并识别可能催化所枚举生化转化的酶结构域。在本文中，我们首先简要概述目前用于分析次生代谢物生物合成途径的工具和方法。我们还讨论了我们在开发用于生化转化逆向生物合成枚举的算法方面的初步工作，以制定一种用于识别与给定聚酮化合物或非核糖体肽生物合成相关基因的新颖计算方法。
