Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs

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....

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Main Authors: Helene L. Robertsen, Ewa M. Musiol-Kroll
Format: Article
Language:English
Published: MDPI AG 2019-09-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/8/4/157
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author Helene L. Robertsen
Ewa M. Musiol-Kroll
author_facet Helene L. Robertsen
Ewa M. Musiol-Kroll
author_sort Helene L. Robertsen
collection DOAJ
description 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.
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spelling doaj.art-6c7ddf8b51a0486caefaf616daccb92f2022-12-21T19:40:41ZengMDPI AGAntibiotics2079-63822019-09-018415710.3390/antibiotics8040157antibiotics8040157Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial DrugsHelene L. Robertsen0Ewa M. Musiol-Kroll1Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, GermanyInterfakultäres Institut für Mikrobiologie und Infektionsmedizin, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, GermanyActinomycetes 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.https://www.mdpi.com/2079-6382/8/4/157actinomycetesbioactivityantimicrobialspolyketidespolyketide synthasesbiosynthesis
spellingShingle Helene L. Robertsen
Ewa M. Musiol-Kroll
Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs
Antibiotics
actinomycetes
bioactivity
antimicrobials
polyketides
polyketide synthases
biosynthesis
title Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs
title_full Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs
title_fullStr Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs
title_full_unstemmed Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs
title_short Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs
title_sort actinomycete derived polyketides as a source of antibiotics and lead structures for the development of new antimicrobial drugs
topic actinomycetes
bioactivity
antimicrobials
polyketides
polyketide synthases
biosynthesis
url https://www.mdpi.com/2079-6382/8/4/157
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