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Engineering actinomycetes for biosynthesis of macrolactone polyketides
Actinobacteria are characterized as the most prominent producer of natural products (NPs) with pharmaceutical importance. The production of NPs from these actinobacteria is associated with particular biosynthetic gene clusters (BGCs) in these microorganisms. The majority of these BGCs include polyke...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693128/ https://www.ncbi.nlm.nih.gov/pubmed/31409353 http://dx.doi.org/10.1186/s12934-019-1184-z |
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author | Dhakal, Dipesh Sohng, Jae Kyung Pandey, Ramesh Prasad |
author_facet | Dhakal, Dipesh Sohng, Jae Kyung Pandey, Ramesh Prasad |
author_sort | Dhakal, Dipesh |
collection | PubMed |
description | Actinobacteria are characterized as the most prominent producer of natural products (NPs) with pharmaceutical importance. The production of NPs from these actinobacteria is associated with particular biosynthetic gene clusters (BGCs) in these microorganisms. The majority of these BGCs include polyketide synthase (PKS) or non-ribosomal peptide synthase (NRPS) or a combination of both PKS and NRPS. Macrolides compounds contain a core macro-lactone ring (aglycone) decorated with diverse functional groups in their chemical structures. The aglycon is generated by megaenzyme polyketide synthases (PKSs) from diverse acyl-CoA as precursor substrates. Further, post-PKS enzymes are responsible for allocating the structural diversity and functional characteristics for their biological activities. Macrolides are biologically important for their uses in therapeutics as antibiotics, anti-tumor agents, immunosuppressants, anti-parasites and many more. Thus, precise genetic/metabolic engineering of actinobacteria along with the application of various chemical/biological approaches have made it plausible for production of macrolides in industrial scale or generation of their novel derivatives with more effective biological properties. In this review, we have discussed versatile approaches for generating a wide range of macrolide structures by engineering the PKS and post-PKS cascades at either enzyme or cellular level in actinobacteria species, either the native or heterologous producer strains. |
format | Online Article Text |
id | pubmed-6693128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66931282019-08-16 Engineering actinomycetes for biosynthesis of macrolactone polyketides Dhakal, Dipesh Sohng, Jae Kyung Pandey, Ramesh Prasad Microb Cell Fact Review Actinobacteria are characterized as the most prominent producer of natural products (NPs) with pharmaceutical importance. The production of NPs from these actinobacteria is associated with particular biosynthetic gene clusters (BGCs) in these microorganisms. The majority of these BGCs include polyketide synthase (PKS) or non-ribosomal peptide synthase (NRPS) or a combination of both PKS and NRPS. Macrolides compounds contain a core macro-lactone ring (aglycone) decorated with diverse functional groups in their chemical structures. The aglycon is generated by megaenzyme polyketide synthases (PKSs) from diverse acyl-CoA as precursor substrates. Further, post-PKS enzymes are responsible for allocating the structural diversity and functional characteristics for their biological activities. Macrolides are biologically important for their uses in therapeutics as antibiotics, anti-tumor agents, immunosuppressants, anti-parasites and many more. Thus, precise genetic/metabolic engineering of actinobacteria along with the application of various chemical/biological approaches have made it plausible for production of macrolides in industrial scale or generation of their novel derivatives with more effective biological properties. In this review, we have discussed versatile approaches for generating a wide range of macrolide structures by engineering the PKS and post-PKS cascades at either enzyme or cellular level in actinobacteria species, either the native or heterologous producer strains. BioMed Central 2019-08-13 /pmc/articles/PMC6693128/ /pubmed/31409353 http://dx.doi.org/10.1186/s12934-019-1184-z Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Dhakal, Dipesh Sohng, Jae Kyung Pandey, Ramesh Prasad Engineering actinomycetes for biosynthesis of macrolactone polyketides |
title | Engineering actinomycetes for biosynthesis of macrolactone polyketides |
title_full | Engineering actinomycetes for biosynthesis of macrolactone polyketides |
title_fullStr | Engineering actinomycetes for biosynthesis of macrolactone polyketides |
title_full_unstemmed | Engineering actinomycetes for biosynthesis of macrolactone polyketides |
title_short | Engineering actinomycetes for biosynthesis of macrolactone polyketides |
title_sort | engineering actinomycetes for biosynthesis of macrolactone polyketides |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693128/ https://www.ncbi.nlm.nih.gov/pubmed/31409353 http://dx.doi.org/10.1186/s12934-019-1184-z |
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