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Roles of type II thioesterases and their application for secondary metabolite yield improvement
A large number of antibiotics and other industrially important microbial secondary metabolites are synthesized by polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). These multienzymatic complexes provide an enormous flexibility in formation of diverse chemical structures from...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147253/ https://www.ncbi.nlm.nih.gov/pubmed/25081554 http://dx.doi.org/10.1007/s00253-014-5952-8 |
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author | Kotowska, Magdalena Pawlik, Krzysztof |
author_facet | Kotowska, Magdalena Pawlik, Krzysztof |
author_sort | Kotowska, Magdalena |
collection | PubMed |
description | A large number of antibiotics and other industrially important microbial secondary metabolites are synthesized by polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). These multienzymatic complexes provide an enormous flexibility in formation of diverse chemical structures from simple substrates, such as carboxylic acids and amino acids. Modular PKSs and NRPSs, often referred to as megasynthases, have brought about a special interest due to the colinearity between enzymatic domains in the proteins working as an “assembly line” and the chain elongation and modification steps. Extensive efforts toward modified compound biosynthesis by changing organization of PKS and NRPS domains in a combinatorial manner laid good grounds for rational design of new structures and their controllable biosynthesis as proposed by the synthetic biology approach. Despite undeniable progress made in this field, the yield of such “unnatural” natural products is often not satisfactory. Here, we focus on type II thioesterases (TEIIs)—discrete hydrolytic enzymes often encoded within PKS and NRPS gene clusters which can be used to enhance product yield. We review diverse roles of TEIIs (removal of aberrant residues blocking the megasynthase, participation in substrate selection, intermediate, and product release) and discuss their application in new biosynthetic systems utilizing PKS and NRPS parts. |
format | Online Article Text |
id | pubmed-4147253 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-41472532014-08-28 Roles of type II thioesterases and their application for secondary metabolite yield improvement Kotowska, Magdalena Pawlik, Krzysztof Appl Microbiol Biotechnol Mini-Review A large number of antibiotics and other industrially important microbial secondary metabolites are synthesized by polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). These multienzymatic complexes provide an enormous flexibility in formation of diverse chemical structures from simple substrates, such as carboxylic acids and amino acids. Modular PKSs and NRPSs, often referred to as megasynthases, have brought about a special interest due to the colinearity between enzymatic domains in the proteins working as an “assembly line” and the chain elongation and modification steps. Extensive efforts toward modified compound biosynthesis by changing organization of PKS and NRPS domains in a combinatorial manner laid good grounds for rational design of new structures and their controllable biosynthesis as proposed by the synthetic biology approach. Despite undeniable progress made in this field, the yield of such “unnatural” natural products is often not satisfactory. Here, we focus on type II thioesterases (TEIIs)—discrete hydrolytic enzymes often encoded within PKS and NRPS gene clusters which can be used to enhance product yield. We review diverse roles of TEIIs (removal of aberrant residues blocking the megasynthase, participation in substrate selection, intermediate, and product release) and discuss their application in new biosynthetic systems utilizing PKS and NRPS parts. Springer Berlin Heidelberg 2014-08-02 2014 /pmc/articles/PMC4147253/ /pubmed/25081554 http://dx.doi.org/10.1007/s00253-014-5952-8 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Mini-Review Kotowska, Magdalena Pawlik, Krzysztof Roles of type II thioesterases and their application for secondary metabolite yield improvement |
title | Roles of type II thioesterases and their application for secondary metabolite yield improvement |
title_full | Roles of type II thioesterases and their application for secondary metabolite yield improvement |
title_fullStr | Roles of type II thioesterases and their application for secondary metabolite yield improvement |
title_full_unstemmed | Roles of type II thioesterases and their application for secondary metabolite yield improvement |
title_short | Roles of type II thioesterases and their application for secondary metabolite yield improvement |
title_sort | roles of type ii thioesterases and their application for secondary metabolite yield improvement |
topic | Mini-Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147253/ https://www.ncbi.nlm.nih.gov/pubmed/25081554 http://dx.doi.org/10.1007/s00253-014-5952-8 |
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