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Co-expression of a SARP Family Activator ChlF2 and a Type II Thioesterase ChlK Led to High Production of Chlorothricin in Streptomyces antibioticus DSM 40725

Chlorothricin (CHL), produced by Streptomyces antibioticus DSM 40725 (wild-type strain, WT), belongs to a growing family of spirotetronate antibiotics that have biological activities inhibiting pyruvate carboxylase and malate dehydrogenase. ChlF2, a cluster-situated SARP regulator, can activate the...

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Autores principales: Li, Yue, Zhang, Jihui, Zheng, Jiazhen, Guan, Hanye, Liu, Wen, Tan, Huarong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471628/
https://www.ncbi.nlm.nih.gov/pubmed/32974326
http://dx.doi.org/10.3389/fbioe.2020.01013
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author Li, Yue
Zhang, Jihui
Zheng, Jiazhen
Guan, Hanye
Liu, Wen
Tan, Huarong
author_facet Li, Yue
Zhang, Jihui
Zheng, Jiazhen
Guan, Hanye
Liu, Wen
Tan, Huarong
author_sort Li, Yue
collection PubMed
description Chlorothricin (CHL), produced by Streptomyces antibioticus DSM 40725 (wild-type strain, WT), belongs to a growing family of spirotetronate antibiotics that have biological activities inhibiting pyruvate carboxylase and malate dehydrogenase. ChlF2, a cluster-situated SARP regulator, can activate the transcription of chlJ, chlC3, chlC6, chlE1, chlM, and chlL to control CHL biosynthesis. Co-expression of chlF2 and chlK encoding type II thioesterase in WT strain under the control of P(kan) led to high production of chlorothricin by 840% in comparison with that of WT. Since the inhibitory activity of CHL against several Gram-positive bacteria is higher than des-CHL, combinatorial strategies were applied to promote the conversion of des-CHL to CHL. Over-expression of chlB4, encoding a halogenase, combining with the supplementation of sodium chloride led to further 41% increase of CHL production compared to that of F2OE, a chlF2 over-expression strain. These findings provide new insights into the fine-tuned regulation of spirotetronate family of antibiotics and the construction of high-yield engineered strains.
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spelling pubmed-74716282020-09-23 Co-expression of a SARP Family Activator ChlF2 and a Type II Thioesterase ChlK Led to High Production of Chlorothricin in Streptomyces antibioticus DSM 40725 Li, Yue Zhang, Jihui Zheng, Jiazhen Guan, Hanye Liu, Wen Tan, Huarong Front Bioeng Biotechnol Bioengineering and Biotechnology Chlorothricin (CHL), produced by Streptomyces antibioticus DSM 40725 (wild-type strain, WT), belongs to a growing family of spirotetronate antibiotics that have biological activities inhibiting pyruvate carboxylase and malate dehydrogenase. ChlF2, a cluster-situated SARP regulator, can activate the transcription of chlJ, chlC3, chlC6, chlE1, chlM, and chlL to control CHL biosynthesis. Co-expression of chlF2 and chlK encoding type II thioesterase in WT strain under the control of P(kan) led to high production of chlorothricin by 840% in comparison with that of WT. Since the inhibitory activity of CHL against several Gram-positive bacteria is higher than des-CHL, combinatorial strategies were applied to promote the conversion of des-CHL to CHL. Over-expression of chlB4, encoding a halogenase, combining with the supplementation of sodium chloride led to further 41% increase of CHL production compared to that of F2OE, a chlF2 over-expression strain. These findings provide new insights into the fine-tuned regulation of spirotetronate family of antibiotics and the construction of high-yield engineered strains. Frontiers Media S.A. 2020-08-21 /pmc/articles/PMC7471628/ /pubmed/32974326 http://dx.doi.org/10.3389/fbioe.2020.01013 Text en Copyright © 2020 Li, Zhang, Zheng, Guan, Liu and Tan. 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
Li, Yue
Zhang, Jihui
Zheng, Jiazhen
Guan, Hanye
Liu, Wen
Tan, Huarong
Co-expression of a SARP Family Activator ChlF2 and a Type II Thioesterase ChlK Led to High Production of Chlorothricin in Streptomyces antibioticus DSM 40725
title Co-expression of a SARP Family Activator ChlF2 and a Type II Thioesterase ChlK Led to High Production of Chlorothricin in Streptomyces antibioticus DSM 40725
title_full Co-expression of a SARP Family Activator ChlF2 and a Type II Thioesterase ChlK Led to High Production of Chlorothricin in Streptomyces antibioticus DSM 40725
title_fullStr Co-expression of a SARP Family Activator ChlF2 and a Type II Thioesterase ChlK Led to High Production of Chlorothricin in Streptomyces antibioticus DSM 40725
title_full_unstemmed Co-expression of a SARP Family Activator ChlF2 and a Type II Thioesterase ChlK Led to High Production of Chlorothricin in Streptomyces antibioticus DSM 40725
title_short Co-expression of a SARP Family Activator ChlF2 and a Type II Thioesterase ChlK Led to High Production of Chlorothricin in Streptomyces antibioticus DSM 40725
title_sort co-expression of a sarp family activator chlf2 and a type ii thioesterase chlk led to high production of chlorothricin in streptomyces antibioticus dsm 40725
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471628/
https://www.ncbi.nlm.nih.gov/pubmed/32974326
http://dx.doi.org/10.3389/fbioe.2020.01013
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