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Sample Preparation of Mycobacterium tuberculosis Extracts for Nuclear Magnetic Resonance Metabolomic Studies
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Saprophytic to Pathogenic Mycobacteria: Loss of Cytochrome P450s Vis a Vis Their Prominent Involvement in Natural

Ntokozo Minenhle Zondo1, Tiara Padayachee1, David R Nelson2

  • 1Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Zululand, KwaDlangezwa 3886, South Africa.

International Journal of Molecular Sciences
|January 8, 2023
PubMed

Insights

Cytochrome P450s (CYPs) are vital enzymes in mycobacteria for producing natural metabolites. Pathogenic strains utilize more CYPs for survival, indicating their role in adaptation and niche colonization.

Area of Science:

  • Microbiology
  • Biochemistry
  • Genomics

Background:

  • Cytochrome P450 monooxygenases (P450s/CYPs) are crucial enzymes for regio- and stereo-selective oxidation.
  • These enzymes are key players in the biosynthesis of natural metabolites, essential for organism survival.
  • Mycobacterial species are known for producing complex metabolites that aid survival in various environments, including host organisms.

Purpose of the Study:

  • To conduct a comprehensive analysis of P450s in mycobacterial species.
  • To investigate the role of P450s in the synthesis of natural metabolites within these bacteria.
  • To understand the evolutionary patterns and functional significance of P450s in mycobacterial adaptation.

Main Methods:

  • Bioinformatic analysis of P450s across 2666 mycobacterial species.
  • Identification and classification of P450 families and subfamilies.
  • Comparative analysis of P450 profiles between non-pathogenic and pathogenic mycobacteria.

Main Results:

  • Discovery of 62,815 P450s, categorized into 182 families and 345 subfamilies.
  • Observation of gene blooming and expansion within P450 families and subfamilies, with CYP135 being dominant.
  • Distinct P450 profiles across mycobacterial species, correlating with lifestyle and pathogenicity.
  • Pathogenic mycobacteria exhibit an enrichment of P450s within biosynthetic gene clusters for natural metabolites.

Conclusions:

  • Mycobacterial P450 profiles are shaped by lifestyle and adaptation.
  • P450s are integral to the biosynthesis of unique metabolites, conferring survival advantages to pathogenic mycobacteria.
  • This study provides the first extensive analysis of P450s and their role in natural product synthesis across a wide range of mycobacterial species.
Keywords:
Mycobacterium tuberculosisadaptationbiosynthetic gene clusterscomplex metabolitescytochrome P450 monooxygenasesecological nichesnatural productpathogenssecondary metabolism

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