Mycofactocin is a member of the rapidly growing class of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products. Although the mycofactocin biosynthetic pathway is widely distributed among Mycobacterial species, the structure, function, and biosynthesis of the pathway product remain unknown. This mini-review will discuss the current state of knowledge regarding the mycofactocin biosynthetic pathway. In particular, we focus on the architecture and distribution of the mycofactocin biosynthetic cluster, mftABCDEF, among the Actinobacteria phylum. We discuss the potential molecular and physiological role of mycofactocin. We review known biosynthetic steps involving MftA, MftB, MftC, and MftE and relate them to pyrroloquinoline quinone biosynthesis. Lastly, we propose the function of the remaining putative biosynthetic enzymes, MftD and MftF.
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http://dx.doi.org/10.1007/s00253-019-09684-4 | DOI Listing |
Elife
January 2025
Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Junior Research Group Synthetic Microbiology, Jena, Germany.
Mycofactocin is a redox cofactor essential for the alcohol metabolism of mycobacteria. While the biosynthesis of mycofactocin is well established, the gene , which encodes an oxidoreductase of the glucose-methanol-choline superfamily, remained functionally uncharacterized. Here, we show that MftG enzymes are almost exclusively found in genomes containing mycofactocin biosynthetic genes and are present in 75% of organisms harboring these genes.
View Article and Find Full Text PDFWorld J Microbiol Biotechnol
January 2025
Shandong Provincial Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, 72 Binhai Road, Jimo, Qingdao, 266237, China.
Catabolic plasmids are critical factors in the degradation of recalcitrant xenobiotics, such as dioxins. Understanding the persistence and evolution of native catabolic plasmids is pivotal for controlling their function in microbial remediation. Here, we track the fitness and evolution of Rhodococcus sp.
View Article and Find Full Text PDFFASEB J
June 2024
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China.
Mycobacterium tuberculosis, the pathogen of the deadly disease tuberculosis, depends on the redox cofactor mycofactocin (MFT) to adapt to and survive under hypoxic conditions. MftR is a TetR family transcription regulator that binds upstream of the MFT gene cluster and controls MFT synthesis. To elucidate the structural basis underlying MftR regulation, we determined the crystal structure of Mycobacterium tuberculosis MftR (TB-MftR).
View Article and Find Full Text PDFAppl Environ Microbiol
July 2024
Department of Microbiology and Immunology, Life Sciences Institute, The University of British Columbia, Vancouver, British Columbia, Canada.
Ethylene glycol (EG) is a widely used industrial chemical with manifold applications and also generated in the degradation of plastics such as polyethylene terephthalate. RHA1 (RHA1), a potential biocatalytic chassis, grows on EG. Transcriptomic analyses revealed four clusters of genes potentially involved in EG catabolism: the locus, predicted to encode ycofactocin-dependent lcohol egradation, including the catabolism of EG to glycolate; two GCL clusters, predicted to encode glycolate and glyoxylate catabolism; and the genes, predicted to specify mycofactocin biosynthesis.
View Article and Find Full Text PDFAppl Microbiol Biotechnol
December 2024
Research Institute of Innovative Technology for the Earth, 9-2, Kizugawadai, Kizugawa-Shi, Kyoto, 619-0292, Japan.
Ethylene glycol is an industrially important diol in many manufacturing processes and a building block of polymers, such as poly(ethylene terephthalate). In this study, we found that a mycolic acid-containing bacterium Rhodococcus jostii RHA1 can grow with ethylene glycol as a sole source of carbon and energy. Deletion of a putative glycolate dehydrogenase gene (RHA1_ro03227) abolished growth with ethylene glycol, indicating that ethylene glycol is assimilated via glycolate in R.
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