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Loss of Serine-Type D-Ala-D-Ala Carboxypeptidase DacA Enhances Prodigiosin Production in Serratia marcescens

Serratia marcescens, a gram-negative bacterium, found in a wide range of ecological niches can produce several high-value products, including prodigiosin, althiomycin, and serratamolide. Among them, prodigiosin has attracted attention due to its immunosuppressive, antimicrobial, and anticancer prope...

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Autores principales: Pan, Xuewei, Sun, Changhao, Tang, Mi, Liu, Chao, Zhang, Jianing, You, Jiajia, Osire, Tolbert, Sun, Yang, Zhao, Youxi, Xu, Meijuan, Yang, Taowei, Rao, Zhiming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901396/
https://www.ncbi.nlm.nih.gov/pubmed/31850328
http://dx.doi.org/10.3389/fbioe.2019.00367
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author Pan, Xuewei
Sun, Changhao
Tang, Mi
Liu, Chao
Zhang, Jianing
You, Jiajia
Osire, Tolbert
Sun, Yang
Zhao, Youxi
Xu, Meijuan
Yang, Taowei
Rao, Zhiming
author_facet Pan, Xuewei
Sun, Changhao
Tang, Mi
Liu, Chao
Zhang, Jianing
You, Jiajia
Osire, Tolbert
Sun, Yang
Zhao, Youxi
Xu, Meijuan
Yang, Taowei
Rao, Zhiming
author_sort Pan, Xuewei
collection PubMed
description Serratia marcescens, a gram-negative bacterium, found in a wide range of ecological niches can produce several high-value products, including prodigiosin, althiomycin, and serratamolide. Among them, prodigiosin has attracted attention due to its immunosuppressive, antimicrobial, and anticancer properties. However, the regulatory mechanisms behind prodigiosin synthesis in Serratia marcescens remains limited. Here, a transposon mutant library was constructed to identify the genes related to prodigiosin synthesis, and BVG90_02415 gene encoding a peptidoglycan synthesizing enzyme D-Ala-D-Ala carboxypeptidase DacA was found to negatively regulates prodigiosin synthesis. Quantitative measurements revealed that disruption of dacA increased prodigiosin production 1.46-fold that of the wild-type strain JNB5-1 in fermentation medium. By comparing differences in cell growth, pigA gene expression level, cell morphology, membrane permeability, and intracellular prodigiosin concentration between wild-type strain JNB5-1 and dacA mutant SK4-72, results revealed that the mechanism for hyper-producing of prodigiosin by the dacA mutant was probably that dacA disruption enhanced prodigiosin leakage, which in turn alleviated feedback inhibition of prodigiosin and increased expression of pig gene cluster. Collectively, this work provides a novel insight into regulatory mechanisms of prodigiosin synthesis and uncovers new roles of DacA protein in regulating cell growth, cell morphology, and membrane permeability in Serratia marcescens. Finally, this study offers a new strategy for improving production of high-value compounds in Serratia marcescens.
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spelling pubmed-69013962019-12-17 Loss of Serine-Type D-Ala-D-Ala Carboxypeptidase DacA Enhances Prodigiosin Production in Serratia marcescens Pan, Xuewei Sun, Changhao Tang, Mi Liu, Chao Zhang, Jianing You, Jiajia Osire, Tolbert Sun, Yang Zhao, Youxi Xu, Meijuan Yang, Taowei Rao, Zhiming Front Bioeng Biotechnol Bioengineering and Biotechnology Serratia marcescens, a gram-negative bacterium, found in a wide range of ecological niches can produce several high-value products, including prodigiosin, althiomycin, and serratamolide. Among them, prodigiosin has attracted attention due to its immunosuppressive, antimicrobial, and anticancer properties. However, the regulatory mechanisms behind prodigiosin synthesis in Serratia marcescens remains limited. Here, a transposon mutant library was constructed to identify the genes related to prodigiosin synthesis, and BVG90_02415 gene encoding a peptidoglycan synthesizing enzyme D-Ala-D-Ala carboxypeptidase DacA was found to negatively regulates prodigiosin synthesis. Quantitative measurements revealed that disruption of dacA increased prodigiosin production 1.46-fold that of the wild-type strain JNB5-1 in fermentation medium. By comparing differences in cell growth, pigA gene expression level, cell morphology, membrane permeability, and intracellular prodigiosin concentration between wild-type strain JNB5-1 and dacA mutant SK4-72, results revealed that the mechanism for hyper-producing of prodigiosin by the dacA mutant was probably that dacA disruption enhanced prodigiosin leakage, which in turn alleviated feedback inhibition of prodigiosin and increased expression of pig gene cluster. Collectively, this work provides a novel insight into regulatory mechanisms of prodigiosin synthesis and uncovers new roles of DacA protein in regulating cell growth, cell morphology, and membrane permeability in Serratia marcescens. Finally, this study offers a new strategy for improving production of high-value compounds in Serratia marcescens. Frontiers Media S.A. 2019-12-03 /pmc/articles/PMC6901396/ /pubmed/31850328 http://dx.doi.org/10.3389/fbioe.2019.00367 Text en Copyright © 2019 Pan, Sun, Tang, Liu, Zhang, You, Osire, Sun, Zhao, Xu, Yang and Rao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Pan, Xuewei
Sun, Changhao
Tang, Mi
Liu, Chao
Zhang, Jianing
You, Jiajia
Osire, Tolbert
Sun, Yang
Zhao, Youxi
Xu, Meijuan
Yang, Taowei
Rao, Zhiming
Loss of Serine-Type D-Ala-D-Ala Carboxypeptidase DacA Enhances Prodigiosin Production in Serratia marcescens
title Loss of Serine-Type D-Ala-D-Ala Carboxypeptidase DacA Enhances Prodigiosin Production in Serratia marcescens
title_full Loss of Serine-Type D-Ala-D-Ala Carboxypeptidase DacA Enhances Prodigiosin Production in Serratia marcescens
title_fullStr Loss of Serine-Type D-Ala-D-Ala Carboxypeptidase DacA Enhances Prodigiosin Production in Serratia marcescens
title_full_unstemmed Loss of Serine-Type D-Ala-D-Ala Carboxypeptidase DacA Enhances Prodigiosin Production in Serratia marcescens
title_short Loss of Serine-Type D-Ala-D-Ala Carboxypeptidase DacA Enhances Prodigiosin Production in Serratia marcescens
title_sort loss of serine-type d-ala-d-ala carboxypeptidase daca enhances prodigiosin production in serratia marcescens
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901396/
https://www.ncbi.nlm.nih.gov/pubmed/31850328
http://dx.doi.org/10.3389/fbioe.2019.00367
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