GdmRIII, a TetR Family Transcriptional Regulator, Controls Geldanamycin and Elaiophylin Biosynthesis in Streptomyces autolyticus CGMCC0516

Abstract Geldanamycin and elaiophylin are co-produced in several Streptomyces strains. However, the regulation of their biosynthesis is not fully understood yet. Herein the function of a TetR family regulator GdmRIII, which is located in the biosynthetic gene cluster of geldanamycin, was studied to...

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Main Authors: MingXing Jiang, Min Yin, ShaoHua Wu, XiuLin Han, KaiYan Ji, MengLiang Wen, Tao Lu
Format: Article
Language:English
Published: Nature Portfolio 2017-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-05073-x
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author MingXing Jiang
Min Yin
ShaoHua Wu
XiuLin Han
KaiYan Ji
MengLiang Wen
Tao Lu
author_facet MingXing Jiang
Min Yin
ShaoHua Wu
XiuLin Han
KaiYan Ji
MengLiang Wen
Tao Lu
author_sort MingXing Jiang
collection DOAJ
description Abstract Geldanamycin and elaiophylin are co-produced in several Streptomyces strains. However, the regulation of their biosynthesis is not fully understood yet. Herein the function of a TetR family regulator GdmRIII, which is located in the biosynthetic gene cluster of geldanamycin, was studied to understand the regulatory mechanism of geldanamycin biosynthesis in Streptomyces autolyticus CGMCC0516. The production of geldanamycin decreased substantially in a ΔgdmRIII mutant and the yield of three compounds which were thought to be geldanamycin congeners greatly increased. Surprisingly, the structural elucidation of these compounds showed that they were elaiophylin and its analogues, which implied that GdmRIII not only played a positive regulatory role in the biosynthesis of geldanamycin, but also played a negative role in elaiophylin biosynthesis. GdmRIII affected the expression of multiple genes in both gene clusters, and directly regulated the expression of gdmM, gdmN, and elaF by binding to the promoter regions of these three genes. A conserved non-palindromic sequence was found among the binding sites of elaF. Our findings suggested that the biosynthetic pathways of geldanamycin and elaiophylin were connected through GdmRIII, which might provide a way for Streptomyces to coordinate the biosynthesis of these compounds for better adapting to environment changes.
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spelling doaj.art-a9bc8de3c92749c68604de3853dc9da52022-12-21T21:20:40ZengNature PortfolioScientific Reports2045-23222017-07-017111110.1038/s41598-017-05073-xGdmRIII, a TetR Family Transcriptional Regulator, Controls Geldanamycin and Elaiophylin Biosynthesis in Streptomyces autolyticus CGMCC0516MingXing Jiang0Min Yin1ShaoHua Wu2XiuLin Han3KaiYan Ji4MengLiang Wen5Tao Lu6Yunnan Institute of Microbiology, Yunnan UniversityYunnan Institute of Microbiology, Yunnan UniversityYunnan Institute of Microbiology, Yunnan UniversityYunnan Institute of Microbiology, Yunnan UniversityYunnan Institute of Microbiology, Yunnan UniversityYunnan Institute of Microbiology, Yunnan UniversityYunnan Institute of Microbiology, Yunnan UniversityAbstract Geldanamycin and elaiophylin are co-produced in several Streptomyces strains. However, the regulation of their biosynthesis is not fully understood yet. Herein the function of a TetR family regulator GdmRIII, which is located in the biosynthetic gene cluster of geldanamycin, was studied to understand the regulatory mechanism of geldanamycin biosynthesis in Streptomyces autolyticus CGMCC0516. The production of geldanamycin decreased substantially in a ΔgdmRIII mutant and the yield of three compounds which were thought to be geldanamycin congeners greatly increased. Surprisingly, the structural elucidation of these compounds showed that they were elaiophylin and its analogues, which implied that GdmRIII not only played a positive regulatory role in the biosynthesis of geldanamycin, but also played a negative role in elaiophylin biosynthesis. GdmRIII affected the expression of multiple genes in both gene clusters, and directly regulated the expression of gdmM, gdmN, and elaF by binding to the promoter regions of these three genes. A conserved non-palindromic sequence was found among the binding sites of elaF. Our findings suggested that the biosynthetic pathways of geldanamycin and elaiophylin were connected through GdmRIII, which might provide a way for Streptomyces to coordinate the biosynthesis of these compounds for better adapting to environment changes.https://doi.org/10.1038/s41598-017-05073-x
spellingShingle MingXing Jiang
Min Yin
ShaoHua Wu
XiuLin Han
KaiYan Ji
MengLiang Wen
Tao Lu
GdmRIII, a TetR Family Transcriptional Regulator, Controls Geldanamycin and Elaiophylin Biosynthesis in Streptomyces autolyticus CGMCC0516
Scientific Reports
title GdmRIII, a TetR Family Transcriptional Regulator, Controls Geldanamycin and Elaiophylin Biosynthesis in Streptomyces autolyticus CGMCC0516
title_full GdmRIII, a TetR Family Transcriptional Regulator, Controls Geldanamycin and Elaiophylin Biosynthesis in Streptomyces autolyticus CGMCC0516
title_fullStr GdmRIII, a TetR Family Transcriptional Regulator, Controls Geldanamycin and Elaiophylin Biosynthesis in Streptomyces autolyticus CGMCC0516
title_full_unstemmed GdmRIII, a TetR Family Transcriptional Regulator, Controls Geldanamycin and Elaiophylin Biosynthesis in Streptomyces autolyticus CGMCC0516
title_short GdmRIII, a TetR Family Transcriptional Regulator, Controls Geldanamycin and Elaiophylin Biosynthesis in Streptomyces autolyticus CGMCC0516
title_sort gdmriii a tetr family transcriptional regulator controls geldanamycin and elaiophylin biosynthesis in streptomyces autolyticus cgmcc0516
url https://doi.org/10.1038/s41598-017-05073-x
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