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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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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. |
format | Online Article Text |
id | pubmed-7471628 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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