Expanding Primary Metabolism Helps Generate the Metabolic Robustness To Facilitate Antibiotic Biosynthesis in <italic toggle="yes">Streptomyces</italic>

ABSTRACT The expansion of the genetic repertoire of an organism by gene duplication or horizontal gene transfer (HGT) can aid adaptation. Streptomyces bacteria are prolific producers of bioactive specialized metabolites that have adaptive functions in nature and have found extensive utility in human...

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Autores principales:	Jana K. Schniete, Pablo Cruz-Morales, Nelly Selem-Mojica, Lorena T. Fernández-Martínez, Iain S. Hunter, Francisco Barona-Gómez, Paul A. Hoskisson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	actinobacteria primary metabolism Streptomyces antibiotics evolution pyruvate kinase Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fa63f88793cd4fa6812bf72ef3840462
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spelling	oai:doaj.org-article:fa63f88793cd4fa6812bf72ef38404622021-11-15T15:53:25ZExpanding Primary Metabolism Helps Generate the Metabolic Robustness To Facilitate Antibiotic Biosynthesis in <italic toggle="yes">Streptomyces</italic>10.1128/mBio.02283-172150-7511https://doaj.org/article/fa63f88793cd4fa6812bf72ef38404622018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02283-17https://doaj.org/toc/2150-7511ABSTRACT The expansion of the genetic repertoire of an organism by gene duplication or horizontal gene transfer (HGT) can aid adaptation. Streptomyces bacteria are prolific producers of bioactive specialized metabolites that have adaptive functions in nature and have found extensive utility in human medicine. While the biosynthesis of these specialized metabolites is directed by dedicated biosynthetic gene clusters, little attention has been focused on how these organisms have evolved robustness in their genomes to facilitate the metabolic plasticity required to provide chemical precursors for biosynthesis during the complex metabolic transitions from vegetative growth to specialized metabolite production and sporulation. Here, we examine genetic redundancy in actinobacteria and show that specialized metabolite-producing bacterial families exhibit gene family expansion in primary metabolism. Focusing on a gene duplication event, we show that the two pyruvate kinases in the genome of Streptomyces coelicolor arose by an ancient duplication event and that each has evolved altered enzymatic kinetics, with Pyk1 having a 20-fold-higher kcat than Pyk2 (4,703 s−1 compared to 215 s−1, respectively), and yet both are constitutively expressed. The pyruvate kinase mutants were also found to be compromised in terms of fitness compared to wild-type Streptomyces. These data suggest that expanding gene families can help maintain cell functionality during metabolic perturbation such as nutrient limitation and/or specialized metabolite production. IMPORTANCE The rise of antimicrobial-resistant infections has prompted a resurgence in interest in understanding the production of specialized metabolites, such as antibiotics, by Streptomyces. The presence of multiple genes encoding the same enzymatic function is an aspect of Streptomyces biology that has received little attention; however, understanding how the metabolic expansion influences these organisms can help enhance production of clinically useful molecules. Here, we show that expanding the number of pyruvate kinases enables metabolic adaptation, increases strain fitness, and represents an excellent target for metabolic engineering of industrial specialized metabolite-producing bacteria and the activation of cryptic specialized metabolites.Jana K. SchnietePablo Cruz-MoralesNelly Selem-MojicaLorena T. Fernández-MartínezIain S. HunterFrancisco Barona-GómezPaul A. HoskissonAmerican Society for Microbiologyarticleactinobacteriaprimary metabolismStreptomycesantibioticsevolutionpyruvate kinaseMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	actinobacteria primary metabolism Streptomyces antibiotics evolution pyruvate kinase Microbiology QR1-502
spellingShingle	actinobacteria primary metabolism Streptomyces antibiotics evolution pyruvate kinase Microbiology QR1-502 Jana K. Schniete Pablo Cruz-Morales Nelly Selem-Mojica Lorena T. Fernández-Martínez Iain S. Hunter Francisco Barona-Gómez Paul A. Hoskisson Expanding Primary Metabolism Helps Generate the Metabolic Robustness To Facilitate Antibiotic Biosynthesis in <italic toggle="yes">Streptomyces</italic>
description	ABSTRACT The expansion of the genetic repertoire of an organism by gene duplication or horizontal gene transfer (HGT) can aid adaptation. Streptomyces bacteria are prolific producers of bioactive specialized metabolites that have adaptive functions in nature and have found extensive utility in human medicine. While the biosynthesis of these specialized metabolites is directed by dedicated biosynthetic gene clusters, little attention has been focused on how these organisms have evolved robustness in their genomes to facilitate the metabolic plasticity required to provide chemical precursors for biosynthesis during the complex metabolic transitions from vegetative growth to specialized metabolite production and sporulation. Here, we examine genetic redundancy in actinobacteria and show that specialized metabolite-producing bacterial families exhibit gene family expansion in primary metabolism. Focusing on a gene duplication event, we show that the two pyruvate kinases in the genome of Streptomyces coelicolor arose by an ancient duplication event and that each has evolved altered enzymatic kinetics, with Pyk1 having a 20-fold-higher kcat than Pyk2 (4,703 s−1 compared to 215 s−1, respectively), and yet both are constitutively expressed. The pyruvate kinase mutants were also found to be compromised in terms of fitness compared to wild-type Streptomyces. These data suggest that expanding gene families can help maintain cell functionality during metabolic perturbation such as nutrient limitation and/or specialized metabolite production. IMPORTANCE The rise of antimicrobial-resistant infections has prompted a resurgence in interest in understanding the production of specialized metabolites, such as antibiotics, by Streptomyces. The presence of multiple genes encoding the same enzymatic function is an aspect of Streptomyces biology that has received little attention; however, understanding how the metabolic expansion influences these organisms can help enhance production of clinically useful molecules. Here, we show that expanding the number of pyruvate kinases enables metabolic adaptation, increases strain fitness, and represents an excellent target for metabolic engineering of industrial specialized metabolite-producing bacteria and the activation of cryptic specialized metabolites.
format	article
author	Jana K. Schniete Pablo Cruz-Morales Nelly Selem-Mojica Lorena T. Fernández-Martínez Iain S. Hunter Francisco Barona-Gómez Paul A. Hoskisson
author_facet	Jana K. Schniete Pablo Cruz-Morales Nelly Selem-Mojica Lorena T. Fernández-Martínez Iain S. Hunter Francisco Barona-Gómez Paul A. Hoskisson
author_sort	Jana K. Schniete
title	Expanding Primary Metabolism Helps Generate the Metabolic Robustness To Facilitate Antibiotic Biosynthesis in <italic toggle="yes">Streptomyces</italic>
title_short	Expanding Primary Metabolism Helps Generate the Metabolic Robustness To Facilitate Antibiotic Biosynthesis in <italic toggle="yes">Streptomyces</italic>
title_full	Expanding Primary Metabolism Helps Generate the Metabolic Robustness To Facilitate Antibiotic Biosynthesis in <italic toggle="yes">Streptomyces</italic>
title_fullStr	Expanding Primary Metabolism Helps Generate the Metabolic Robustness To Facilitate Antibiotic Biosynthesis in <italic toggle="yes">Streptomyces</italic>
title_full_unstemmed	Expanding Primary Metabolism Helps Generate the Metabolic Robustness To Facilitate Antibiotic Biosynthesis in <italic toggle="yes">Streptomyces</italic>
title_sort	expanding primary metabolism helps generate the metabolic robustness to facilitate antibiotic biosynthesis in <italic toggle="yes">streptomyces</italic>
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/fa63f88793cd4fa6812bf72ef3840462
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Expanding Primary Metabolism Helps Generate the Metabolic Robustness To Facilitate Antibiotic Biosynthesis in <italic toggle="yes">Streptomyces</italic>

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