Abstract
Actinomycetes are remarkable producers of compounds essential for human and veterinary medicine as well as for agriculture. The genomes of those microorganisms possess several sets of genes (biosynthetic gene cluster (BGC)) encoding pathways for the production of the valuable secondary metabolites. A significant proportion of the identified BGCs in actinomycetes encode pathways for the biosynthesis of polyketide compounds, nonribosomal peptides, or hybrid products resulting from the combination of both polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). The potency of these molecules, in terms of bioactivity, was recognized in the 1940s, and started the “Golden Age” of antimicrobial drug discovery. Since then, several valuable polyketide drugs, such as erythromycin A, tylosin, monensin A, rifamycin, tetracyclines, amphotericin B, and many others were isolated from actinomycetes. This review covers the most relevant actinomycetes-derived polyketide drugs with antimicrobial activity, including anti-fungal agents. We provide an overview of the source of the compounds, structure of the molecules, the biosynthetic principle, bioactivity and mechanisms of action, and the current stage of development. This review emphasizes the importance of actinomycetes-derived antimicrobial polyketides and should serve as a “lexicon”, not only to scientists from the Natural Products field, but also to clinicians and others interested in this topic.
Highlights
More than 70 years has passed since the discovery of the first antibiotics from actinomycetes
Since polyketide-derived antimicrobials have had a historical significance in human therapy, this group of compounds remain important for continuation of research aiming at: the identification of new structures and activities, the biosynthesis and/or chemical semi-synthesis for discovery of novel derivatisation routes, and at understanding of resistance mechanisms to overcome this obstacle
This calls for the discovery and development of new antibiotics and antimicrobial strategies
Summary
More than 70 years has passed since the discovery of the first antibiotics from actinomycetes. Are being put forward in order to limit the further spread of antimicrobial resistance [31] Some of these initiatives include the development of vaccines, faster diagnostic tests to ensure appropriate antibiotic administration, and immune-based therapies [32]. These measures could provide promising solutions for prevention of infections once infection occurs in a human host, antibiotics remain the choice of treatment for bacterial and fungal infections. Since polyketide-derived antimicrobials have had a historical significance in human therapy, this group of compounds remain important for continuation of research aiming at: the identification of new structures and activities, the biosynthesis and/or chemical semi-synthesis for discovery of novel derivatisation routes, and at understanding of resistance mechanisms to overcome this obstacle. This review should serve as a “lexicon” of actinomycetes-derived antimicrobial polyketides, to scientists from the Natural Products field, and to clinicians and others interested in this topic
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