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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...

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Detalles Bibliográficos
Autores principales: Kotowska, Magdalena, Pawlik, Krzysztof
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2014
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.
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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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