Abstract
Bacterial secondary metabolites represent an invaluable source of bioactive molecules for the pharmaceutical and agrochemical industries. Although screening campaigns for the discovery of new compounds have traditionally been strongly biased towards the study of soil-dwelling Actinobacteria, the current antibiotic resistance and discovery crisis has brought a considerable amount of attention to the study of previously neglected bacterial sources of secondary metabolites. The development and application of new screening, sequencing, genetic manipulation, cultivation and bioinformatic techniques have revealed several other groups of bacteria as producers of striking chemical novelty. Biosynthetic machineries evolved from independent taxonomic origins and under completely different ecological requirements and selective pressures are responsible for these structural innovations. In this review, we summarize the most important discoveries related to secondary metabolites from alternative bacterial sources, trying to provide the reader with a broad perspective on how technical novelties have facilitated the access to the bacterial metabolic dark matter.
Highlights
Bacterial specialized metabolites constitute one of the most astonishing expressions of biodiversity, as well as a major source of bioactive molecules for the pharmaceutical and agrochemical industries
The enzymes involved in the biosynthesis of a given natural product are generally encoded by genes compactly grouped within the bacterial genomes, conforming functional units known as biosynthetic genes clusters (BGCs)
In recent years, the antibiotic resistance and discovery crisis [6,7] has triggered radical innovations in the natural products discovery strategies in the search for compounds able to fight the life-threatening infections caused by multidrug-resistant pathogens, as well as to satisfy previously unmet therapeutic needs
Summary
Bacterial specialized metabolites ( known as secondary metabolites or natural products) constitute one of the most astonishing expressions of biodiversity, as well as a major source of bioactive molecules for the pharmaceutical and agrochemical industries. In recent years, the antibiotic resistance and discovery crisis [6,7] has triggered radical innovations in the natural products discovery strategies in the search for compounds able to fight the life-threatening infections caused by multidrug-resistant pathogens (especially those belonging to the ESKAPE group [8]), as well as to satisfy previously unmet therapeutic needs Some of those strategies are focused on the genetic engineering-mediated awakening of silent or cryptic BGCs previously detected by the bioinformatic analysis of bacterial genomes. We summarize the most important achievements in the exploration of new bacterial biodiversity and ecology for the discovery of novel specialized metabolites
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