Cargando…

Respiratory Quinone Switches from Menaquinone to Polyketide Quinone during the Development Cycle in Streptomyces sp. Strain MNU77

Type III polyketide synthases (PKSs) found across Streptomyces species are primarily known for synthesis of a vast repertoire of clinically and industrially relevant secondary metabolites. However, our understanding of the functional relevance of these bioactive metabolites in Streptomyces physiolog...

Descripción completa

Detalles Bibliográficos
Autores principales: Mehdiratta, Kritee, Nain, Sonam, Sharma, Meenakshi, Singh, Shubham, Srivastava, Sonali, Dhamale, Bhushan Dilip, Mohanty, Debasisa, Kamat, Siddhesh S., Natarajan, Vivek T., Sharma, Rakesh, Gokhale, Rajesh S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927152/
https://www.ncbi.nlm.nih.gov/pubmed/36507669
http://dx.doi.org/10.1128/spectrum.02597-22
_version_ 1784888422163283968
author Mehdiratta, Kritee
Nain, Sonam
Sharma, Meenakshi
Singh, Shubham
Srivastava, Sonali
Dhamale, Bhushan Dilip
Mohanty, Debasisa
Kamat, Siddhesh S.
Natarajan, Vivek T.
Sharma, Rakesh
Gokhale, Rajesh S.
author_facet Mehdiratta, Kritee
Nain, Sonam
Sharma, Meenakshi
Singh, Shubham
Srivastava, Sonali
Dhamale, Bhushan Dilip
Mohanty, Debasisa
Kamat, Siddhesh S.
Natarajan, Vivek T.
Sharma, Rakesh
Gokhale, Rajesh S.
author_sort Mehdiratta, Kritee
collection PubMed
description Type III polyketide synthases (PKSs) found across Streptomyces species are primarily known for synthesis of a vast repertoire of clinically and industrially relevant secondary metabolites. However, our understanding of the functional relevance of these bioactive metabolites in Streptomyces physiology is still limited. Recently, a role of type III PKS harboring gene cluster in producing alternate electron carrier, polyketide quinone (PkQ) was established in a related member of the Actinobacteria, Mycobacteria, highlighting the critical role these secondary metabolites play in primary cellular metabolism of the producer organism. Here, we report the developmental stage-specific transcriptional regulation of homologous type III PKS containing gene cluster in freshwater Streptomyces sp. strain MNU77. Gene expression analysis revealed the type III PKS gene cluster to be stringently regulated, with significant upregulation observed during the dormant sporulation stage of Streptomyces sp. MNU77. In contrast, the expression levels of only known electron carrier, menaquinone biosynthetic genes were interestingly found to be downregulated. Our liquid chromatography–high-resolution mass spectrometry (LC-HRMS) analysis of a metabolite extract from the Streptomyces sp. MNU77 spores also showed 10 times more metabolic abundance of PkQs than menaquinones. Furthermore, through heterologous complementation studies, we demonstrate that Streptomyces sp. MNU77 type III PKS rescues a respiratory defect of the Mycobacterium smegmatis type III PKS deletion mutant. Together, our studies reveal that freshwater Streptomyces sp. MNU77 robustly produces novel PkQs during the sporulation stage, suggesting utilization of PkQs as alternate electron carriers across Actinobacteria during dormant hypoxic conditions. IMPORTANCE The complex developmental life cycle of Streptomyces sp. mandates efficient cellular respiratory reconfiguration for a smooth transition from aerated nutrient-rich vegetative hyphal growth to the hypoxic-dormant sporulation stage. Polyketide quinones (PkQs) have recently been identified as a class of alternate electron carriers from a related member of the Actinobacteria, Mycobacteria, that facilitates maintenance of membrane potential in oxygen-deficient niches. Our studies with the newly identified freshwater Streptomyces sp. strain MNU77 show conditional transcriptional upregulation and metabolic abundance of PkQs in the spore state of the Streptomyces life cycle. In parallel, the levels of menaquinones, the only known Streptomyces electron carrier, were downregulated, suggesting deployment of PkQs as universal electron carriers in low-oxygen, unfavorable conditions across the Actinobacteria family.
format Online
Article
Text
id pubmed-9927152
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Society for Microbiology
record_format MEDLINE/PubMed
spelling pubmed-99271522023-02-15 Respiratory Quinone Switches from Menaquinone to Polyketide Quinone during the Development Cycle in Streptomyces sp. Strain MNU77 Mehdiratta, Kritee Nain, Sonam Sharma, Meenakshi Singh, Shubham Srivastava, Sonali Dhamale, Bhushan Dilip Mohanty, Debasisa Kamat, Siddhesh S. Natarajan, Vivek T. Sharma, Rakesh Gokhale, Rajesh S. Microbiol Spectr Research Article Type III polyketide synthases (PKSs) found across Streptomyces species are primarily known for synthesis of a vast repertoire of clinically and industrially relevant secondary metabolites. However, our understanding of the functional relevance of these bioactive metabolites in Streptomyces physiology is still limited. Recently, a role of type III PKS harboring gene cluster in producing alternate electron carrier, polyketide quinone (PkQ) was established in a related member of the Actinobacteria, Mycobacteria, highlighting the critical role these secondary metabolites play in primary cellular metabolism of the producer organism. Here, we report the developmental stage-specific transcriptional regulation of homologous type III PKS containing gene cluster in freshwater Streptomyces sp. strain MNU77. Gene expression analysis revealed the type III PKS gene cluster to be stringently regulated, with significant upregulation observed during the dormant sporulation stage of Streptomyces sp. MNU77. In contrast, the expression levels of only known electron carrier, menaquinone biosynthetic genes were interestingly found to be downregulated. Our liquid chromatography–high-resolution mass spectrometry (LC-HRMS) analysis of a metabolite extract from the Streptomyces sp. MNU77 spores also showed 10 times more metabolic abundance of PkQs than menaquinones. Furthermore, through heterologous complementation studies, we demonstrate that Streptomyces sp. MNU77 type III PKS rescues a respiratory defect of the Mycobacterium smegmatis type III PKS deletion mutant. Together, our studies reveal that freshwater Streptomyces sp. MNU77 robustly produces novel PkQs during the sporulation stage, suggesting utilization of PkQs as alternate electron carriers across Actinobacteria during dormant hypoxic conditions. IMPORTANCE The complex developmental life cycle of Streptomyces sp. mandates efficient cellular respiratory reconfiguration for a smooth transition from aerated nutrient-rich vegetative hyphal growth to the hypoxic-dormant sporulation stage. Polyketide quinones (PkQs) have recently been identified as a class of alternate electron carriers from a related member of the Actinobacteria, Mycobacteria, that facilitates maintenance of membrane potential in oxygen-deficient niches. Our studies with the newly identified freshwater Streptomyces sp. strain MNU77 show conditional transcriptional upregulation and metabolic abundance of PkQs in the spore state of the Streptomyces life cycle. In parallel, the levels of menaquinones, the only known Streptomyces electron carrier, were downregulated, suggesting deployment of PkQs as universal electron carriers in low-oxygen, unfavorable conditions across the Actinobacteria family. American Society for Microbiology 2022-12-12 /pmc/articles/PMC9927152/ /pubmed/36507669 http://dx.doi.org/10.1128/spectrum.02597-22 Text en Copyright © 2022 Mehdiratta et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Mehdiratta, Kritee
Nain, Sonam
Sharma, Meenakshi
Singh, Shubham
Srivastava, Sonali
Dhamale, Bhushan Dilip
Mohanty, Debasisa
Kamat, Siddhesh S.
Natarajan, Vivek T.
Sharma, Rakesh
Gokhale, Rajesh S.
Respiratory Quinone Switches from Menaquinone to Polyketide Quinone during the Development Cycle in Streptomyces sp. Strain MNU77
title Respiratory Quinone Switches from Menaquinone to Polyketide Quinone during the Development Cycle in Streptomyces sp. Strain MNU77
title_full Respiratory Quinone Switches from Menaquinone to Polyketide Quinone during the Development Cycle in Streptomyces sp. Strain MNU77
title_fullStr Respiratory Quinone Switches from Menaquinone to Polyketide Quinone during the Development Cycle in Streptomyces sp. Strain MNU77
title_full_unstemmed Respiratory Quinone Switches from Menaquinone to Polyketide Quinone during the Development Cycle in Streptomyces sp. Strain MNU77
title_short Respiratory Quinone Switches from Menaquinone to Polyketide Quinone during the Development Cycle in Streptomyces sp. Strain MNU77
title_sort respiratory quinone switches from menaquinone to polyketide quinone during the development cycle in streptomyces sp. strain mnu77
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927152/
https://www.ncbi.nlm.nih.gov/pubmed/36507669
http://dx.doi.org/10.1128/spectrum.02597-22
work_keys_str_mv AT mehdirattakritee respiratoryquinoneswitchesfrommenaquinonetopolyketidequinoneduringthedevelopmentcycleinstreptomycesspstrainmnu77
AT nainsonam respiratoryquinoneswitchesfrommenaquinonetopolyketidequinoneduringthedevelopmentcycleinstreptomycesspstrainmnu77
AT sharmameenakshi respiratoryquinoneswitchesfrommenaquinonetopolyketidequinoneduringthedevelopmentcycleinstreptomycesspstrainmnu77
AT singhshubham respiratoryquinoneswitchesfrommenaquinonetopolyketidequinoneduringthedevelopmentcycleinstreptomycesspstrainmnu77
AT srivastavasonali respiratoryquinoneswitchesfrommenaquinonetopolyketidequinoneduringthedevelopmentcycleinstreptomycesspstrainmnu77
AT dhamalebhushandilip respiratoryquinoneswitchesfrommenaquinonetopolyketidequinoneduringthedevelopmentcycleinstreptomycesspstrainmnu77
AT mohantydebasisa respiratoryquinoneswitchesfrommenaquinonetopolyketidequinoneduringthedevelopmentcycleinstreptomycesspstrainmnu77
AT kamatsiddheshs respiratoryquinoneswitchesfrommenaquinonetopolyketidequinoneduringthedevelopmentcycleinstreptomycesspstrainmnu77
AT natarajanvivekt respiratoryquinoneswitchesfrommenaquinonetopolyketidequinoneduringthedevelopmentcycleinstreptomycesspstrainmnu77
AT sharmarakesh respiratoryquinoneswitchesfrommenaquinonetopolyketidequinoneduringthedevelopmentcycleinstreptomycesspstrainmnu77
AT gokhalerajeshs respiratoryquinoneswitchesfrommenaquinonetopolyketidequinoneduringthedevelopmentcycleinstreptomycesspstrainmnu77