Recent advances in genetic manipulation of organisms for the production of nonribosomal peptides

Abstract

Nonribosomal peptides (NRP) are a class of natural products biosynthesized by nonribosomal peptide synthetases (NRPS). These complex multimodular enzymes are present mainly in bacteria and filamentous fungi and each module is responsible for substrates insertion, elongation and chemical modification of the NRP chain. NRP are polypeptides with broad biological activity and the antibiotic property is of especial interest to the pharmaceutical industries in order to fight against one of the biggest challenges of modern medicine: bacterial multiresistance to current available drugs. Over the last years, the NRP biosynthesis have been studied and engineered in order to obtain structural diversity. The advances in molecular biology in the post-genomic era assured the enhancement of already known techniques, such as site-directed mutation, increasing the promiscuity of enzymes, furthermore the introduction of new techniques, as heterologous expression, complete transference of gene clusters to heterologous organisms allowed the identification of new compounds or increasing expression level of already identified products. The present review aims to highlight the relevance of mutasynthesis and heterologous expression for the production of new natural products biosynthesized by NRPS.