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The mycobacterial desaturase DesA2 is associated with mycolic acid biosynthesis

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Bailo, Rebeca, Radhakrishnan, Anjana, Singh, Albel, Nakaya, Makoto, Fujiwara, Nagatoshi and Bhatt, Apoorva (2022) The mycobacterial desaturase DesA2 is associated with mycolic acid biosynthesis. Scientific Reports, 12 (1). 6943. doi:10.1038/s41598-022-10589-y ISSN 2045-2322.

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Official URL: https://doi.org/10.1038/s41598-022-10589-y

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Abstract

Mycolic acids are critical for the survival and virulence of Mycobacterium tuberculosis, the causative agent of tuberculosis. Double bond formation in the merochain of mycolic acids remains poorly understood, though we have previously shown desA1, encoding an aerobic desaturase, is involved in mycolic acid desaturation. Here we show that a second desaturase encoded by desA2 is also involved in mycolate biosynthesis. DesA2 is essential for growth of the fast-growing Mycobacterium smegmatis in laboratory media. Conditional depletion of DesA2 led to a decrease in mycolic acid biosynthesis and loss of mycobacterial viability. Additionally, DesA2-depleted cells also accumulated fatty acids of chain lengths C19-C24. The complete loss of mycolate biosynthesis following DesA2 depletion, and the absence of any monoenoic derivatives (found to accumulate on depletion of DesA1) suggests an early role for DesA2 in the mycolic acid biosynthesis machinery, highlighting its potential as a drug target.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
Q Science > QR Microbiology
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Mycobacterium tuberculosis, Mycobacteria, Biosynthesis -- Research
Journal or Publication Title: Scientific Reports
Publisher: Nature Publishing Group
ISSN: 2045-2322
Official Date: 28 April 2022
Dates:
DateEvent
28 April 2022Published
11 April 2022Accepted
Volume: 12
Number: 1
Article Number: 6943
DOI: 10.1038/s41598-022-10589-y
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 18 May 2022
Date of first compliant Open Access: 18 May 2022
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
BB/N01314X/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
MR/K00042X/1[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/S000542/1[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
Midlands Integrative Biosciences Training PartnershipUniversity of Warwickhttp://dx.doi.org/10.13039/501100000741

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