Abstract

Streptomyces is a diverse group of gram-positive microorganisms characterised by a complex developmental cycle. Streptomycetes produce a number of antibiotics and other bioactive compounds used in the clinic. Most screening campaigns looking for new bioactive molecules from actinomycetes have been performed empirically, e.g., without considering whether the bacteria are growing under the best developmental conditions for secondary metabolite production. These screening campaigns were extremely productive and discovered a number of new bioactive compounds during the so-called “golden age of antibiotics” (until the 1980s). However, at present, there is a worrying bottleneck in drug discovery, and new experimental approaches are needed to improve the screening of natural actinomycetes. Streptomycetes are still the most important natural source of antibiotics and other bioactive compounds. They harbour many cryptic secondary metabolite pathways not expressed under classical laboratory cultures. Here, we review the new strategies that are being explored to overcome current challenges in drug discovery. In particular, we focus on those aimed at improving the differentiation of the antibiotic-producing mycelium stage in the laboratory.

Highlights

  • The Streptomyces genus includes an important group of biotechnological bacteria

  • Streptomyces liquid cultures is the differentiation of MII

  • In the last few years, effort has been made to elucidate the mechanism by which some small molecules affect differentiation and secondary metabolite production in Streptomyces strains

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Summary

Introduction

The Streptomyces genus includes an important group of biotechnological bacteria. They produce two-thirds of the antibiotics of medical and agricultural interest, several antitumor agents, antifungals, and a great number of eukaryotic cell differentiation effectors, such as apoptosis inducers and inhibitors [1]. Most cultures, is a first mycelium (MI), PCD and the differentiation of ametabolite secondaryproduction metabolite, authors there have affirmed that pelletsstage and clumps are fundamental for secondary producing mycelium (MII). Coelicolor proteomic and transcriptomic studies have shown that while some authors have affirmed that pellet and clump formation reduces antibiotic production physiological in liquid solid cultures comparable. Streptomyces liquid cultures is the differentiation of MII (e.g., actinorhodin/undecylprodigiosin production in S. coelicolor [2,13], microbial transglutaminase production in S. mobarensis [14], apigenin and luteolin production in S. albus [15]) The differentiation of this mycelium is conditioned by PCD of the vegetative hyphae (MI) [2], which, in liquid cultures, depends on the growth rate of the strain and hypha aggregation (pellet/clump formation) [2,7,14,15,16]. We review the most important strategies that are being explored to activate cryptic pathways and/or those that are being explored to enhance secondary metabolites production

Screening for New Secondary Metabolites from Streptomycetes
Streptomyces Differentiation Strategies Based on Elicitors
Differentiation Strategies Based on Macroscopic Morphology
L-Forms
Other Strategies
Conclusions
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