title: Polyketide Quinones Are Alternate Intermediate Electron Carriers during Mycobacterial Respiration in Oxygen-Deficient Niches.
abstract: Mycobacterium tuberculosis (Mtb) adaptation to hypoxia is considered crucial to its prolonged latent persistence in humans. Mtb lesions are known to contain physiologically heterogeneous microenvironments that bring about differential responses from bacteria. Here we exploit metabolic variability within biofilm cells to identify alternate respiratory polyketide quinones (PkQs) from both Mycobacterium smegmatis (Msmeg) and Mtb. PkQs are specifically expressed in biofilms and other oxygen-deficient niches to maintain cellular bioenergetics. Under such conditions, these metabolites function as mobile electron carriers in the respiratory electron transport chain. In the absence of PkQs, mycobacteria escape from the hypoxic core of biofilms and prefer oxygen-rich conditions. Unlike the ubiquitous isoprenoid pathway for the biosynthesis of respiratory quinones, PkQs are produced by type III polyketide synthases using fatty acyl-CoA precursors. The biosynthetic pathway is conserved in several other bacterial genomes, and our study reveals a redox-balancing chemicocellular process in microbial physiology.
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110020, India; Academy of Scientific and Innovative Research, Rafi Marg, New Delhi 110001, India.
authors.forename: Amitesh
authors.initials: A
authors.lastname: Anand
authors.affiliation: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Verma
authors.affiliation: CSIR-North East Institute of Science and Technology, Jorhat 785006, India.
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Singh
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110020, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kaushik
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110020, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Pandey
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Ce
authors.initials: C
authors.lastname: Shi
authors.affiliation: Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Harneet
authors.initials: H
authors.lastname: Kaur
authors.affiliation: Department of Microbiology and Cell Biology, Centre for Infectious Disease and Research, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Manbeena
authors.initials: M
authors.lastname: Chawla
authors.affiliation: Academy of Scientific and Innovative Research, Rafi Marg, New Delhi 110001, India; CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Chandra Kumar
authors.initials: CK
authors.lastname: Elechalawar
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110020, India.
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Neel S
authors.initials: NS
authors.lastname: Bhavesh
authors.affiliation: Academy of Scientific and Innovative Research, Rafi Marg, New Delhi 110001, India; CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110020, India.
authors.forename: Debasis
authors.initials: D
authors.lastname: Dash
authors.affiliation: Department of Microbiology and Cell Biology, Centre for Infectious Disease and Research, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Singh
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110020, India.
authors.forename: Vivek T
authors.initials: VT
authors.lastname: Natarajan
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Ojha
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA; Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Courtney C
authors.initials: CC
authors.lastname: Aldrich
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110020, India; Academy of Scientific and Innovative Research, Rafi Marg, New Delhi 110001, India; National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India. Electronic address: rsg@igib.res.in.
authors.forename: Rajesh S
authors.initials: RS
authors.lastname: Gokhale
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D018441:Biofilms; D053898:Biosynthetic Pathways; D015687:Cell Hypoxia; D020102:Mycobacterium smegmatis / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D010084:Oxidation-Reduction; D048630:Polyketide Synthases / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism*
chemical_list: D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D061065:Polyketides; D011809:Quinones; D048630:Polyketide Synthases