The Functional Order (FunOrder) tool – Identification of essential biosynthetic genes through computational molecular co-evolution
bioRxiv(2021)
Abstract
Secondary metabolites (SMs) are a vast group of compounds with different structures and properties. Humankind uses SMs as drugs, food additives, dyes, and as monomers for novel plastics. In many cases, the biosynthesis of SMs is catalysed by enzymes whose corresponding genes are co-localized in the genome in biosynthetic gene clusters (BGCs). Notably, BGCs may contain so-called gap genes, that are not involved in the biosynthesis of the SM. Current genome mining tools can identify BGCs but they have problems with distinguishing essential genes from gap genes and defining the borders of a BGC. This can and must be done by expensive, laborious, and time-consuming comparative genomic approaches or co-expression analyses. In this study, we developed a novel tool that allows automated identification of essential genes in a BGC based solely on genomic data. The Functional Order (FunOrder) tool – Identification of essential biosynthetic genes through computational molecular co-evolution – searches for co-evolutionary linked genes in the BGCs. In light of the growing number of genomic data available, this will contribute to the studies of BGCs in native hosts and facilitate heterologous expression in other organisms with the aim of the discovery of novel SMs, including antibiotics and other pharmaceuticals.
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Key words
essential biosynthetic genes,functional order,co-evolution
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