Mycofactocin is essential for the establishment of methylotrophy in Mycobacterium smegmatis

Dubey, Abhishek Anil; Jain, Vikas

doi:10.1016/j.bbrc.2019.07.008

Cited by 21 publications

(32 citation statements)

References 29 publications

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“…2) showed a fragment ion that corresponded to the mass of the putative aglycon (m/z 236. 13 [M+H] + ), thus supporting the assumption that MFT-1H 2 was a glycosylated derivative of PMFTH 2 . MS/MS networking also revealed a recurrent mass difference of 14.01565 between compounds, indicating that methylation might occur as well.…”

Section: Discovery Of Mycofactocins By Metabolomicssupporting

confidence: 70%

“…Compounds were detected by in-silico grouping of co-eluting isotopic peaks and adducts (feature finding). Afterwards, 13 C-labeled compounds were deduced computationally (Supplementary Table 1). According to the established biosynthetic pathway we expected 13 carbons to remain 13 C-labeled after oxidative decarboxylation of the Val-Tyr core peptide.…”

Section: Discovery Of Mycofactocins By Metabolomicsmentioning

confidence: 99%

“…Filters were incubated at 37 °C for 48 h. Directly after the incubation period, the filters were extracted and subjected to LC-MS measurements as described below. Data analysis was performed with the Stable Isotope Labeling workflow of Compound Discoverer 3.0 (Thermo Scientific) allowing for a maximum exchange of 16 13 C atoms. Independent analyses were performed for the lower and higher scan ranges.…”

Section: Isotopic Labeling Of M Smegmatismentioning

confidence: 99%

“…The inactivation of the MFT gene locus in the model species Mycolicibacterium smegmatis (synonym: Mycobacterium smegmatis) as well as M. tuberculosis resulted in the inability of the mutants to utilize ethanol as a sole source of carbon and further disturbances of mycobacterial redox homeostasis were revealed 12 . Involvement of MFT in methanol metabolism was reported as well 13 . These recent results strongly support the hypothesis that MFT is a redox cofactor and might represent a fitness factor of mycobacteria during some stages of infection.…”

Section: Introductionmentioning

confidence: 97%

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Biosynthesis of the redox cofactor mycofactocin comprises oligoglycosylation by MftF in Mycolicibacterium smegmatis

Peña-Ortiz

Graça

Guo

et al. 2019

Preprint

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Mycofactocin (MFT) is a redox cofactor involved in alcohol metabolism of mycobacteria including Mycobacterium tuberculosis. In recent years, a preliminary biosynthetic model of MFT has been established by in-vitro studies, while the final structure of MFT remained elusive. Here, we report the discovery of MFT by metabolomics and establish a model of its biosynthesis in Mycolicibacterium smegmatis. Structure elucidation revealed that MFT is decorated with up to nine b-1,4-linked glucose residues. Dissection of biosynthetic genes demonstrated that the oligoglycosylation is catalyzed by the glycosyltransferase MftF. Furthermore, we confirm the cofactor function of MFT by activity-based metabolic profiling using the carveol dehydrogenase LimC and show that the MFT pool expands during cultivation on ethanol. Our results close an important gap of knowledge, will guide future studies into the physiological roles of MFT in bacteria and may inspire its utilization as a biomarker or potential drug target to combat mycobacterial diseases.Keywords: Mycofactocin / cofactor / Mycobacterium / metabolomics / mass spectrometry (MS) / alcohol metabolism / drug target

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Section: Discovery Of Mycofactocins By Metabolomicssupporting

confidence: 70%

Section: Discovery Of Mycofactocins By Metabolomicsmentioning

confidence: 99%

Section: Isotopic Labeling Of M Smegmatismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Biosynthesis of the redox cofactor mycofactocin comprises oligoglycosylation by MftF in Mycolicibacterium smegmatis

Peña-Ortiz

Graça

Guo

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Compounds were detected by in silico grouping of coeluting isotopic peaks and adducts (feature nding). Aerwards, 13 C-labeled compounds were deduced computationally (Data Set 1 †). According to the established biosynthetic pathway we expected 13 carbons to remain 13 C-labeled aer oxidative decarboxylation of the Val-Tyr core peptide.…”

Section: Discovery Of Mycofactocins By Metabolomicsmentioning

confidence: 99%

Structure elucidation of the redox cofactor mycofactocin reveals oligo-glycosylation by MftF

et al. 2020

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Ms6244 is a novel Mycobacterium smegmatisTetR family transcriptional repressor that regulates cell growth and morphophysiology

2023

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Transcriptional factors such as the TetR family of transcriptional regulators (TFTRs) are widely found amongst bacteria, including mycobacteria, and are accountable for their survival. Here, we characterized a novel TFTR, Ms6244, from Mycobacterium smegmatis that negatively autoregulates its expression and represses its neighbouring gene, Ms6243. We also report the binding of Ms6244 to the inverted repeats in the intergenic region of Ms6244 and Ms6243. Further, an Ms6244-deleted strain shows various morphophysiological differences compared to the wild type. We further confirmed that the deletion of Ms6244 itself and not the resultant Ms6243 overexpression is the cause of the altered physiology. Our data thus suggest that Ms6244 is an essential regulator, having far-reaching effects on M. smegmatis physiology.

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Mycofactocin is essential for the establishment of methylotrophy in Mycobacterium smegmatis

Cited by 21 publications

References 29 publications

Biosynthesis of the redox cofactor mycofactocin comprises oligoglycosylation by MftF in Mycolicibacterium smegmatis

Biosynthesis of the redox cofactor mycofactocin comprises oligoglycosylation by MftF in Mycolicibacterium smegmatis

Structure elucidation of the redox cofactor mycofactocin reveals oligo-glycosylation by MftF

Ms6244 is a novel Mycobacterium smegmatisTetR family transcriptional repressor that regulates cell growth and morphophysiology

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