Abstract
Tuberculosis (TB) is one of the top infectious diseases causing numerous human deaths in the world. Despite enormous efforts, the physiology of the causative agent, Mycobacterium tuberculosis, is poorly understood. To contribute to better understanding the physiological capacity of these microbes, we have carried out extensive in silico analyses of the 1111 mycobacterial species genomes focusing on revealing the role of the orphan cytochrome P450 monooxygenase (CYP) CYP139 family. We have found that CYP139 members are present in 894 species belonging to three mycobacterial groups: M. tuberculosis complex (850-species), Mycobacterium avium complex (34-species), and non-tuberculosis mycobacteria (10-species), with all CYP139 members belonging to the subfamily “A”. CYP139 members have unique amino acid patterns at the CXG motif. Amino acid conservation analysis placed this family in the 8th among CYP families belonging to different biological domains and kingdoms. Biosynthetic gene cluster analyses have revealed that 92% of CYP139As might be associated with producing different secondary metabolites. Such enhanced secondary metabolic potentials with the involvement of CYP139A members might have provided mycobacterial species with advantageous traits in diverse niches competing with other microbial or viral agents, and might help these microbes infect hosts by interfering with the hosts’ metabolism and immune system.
Highlights
Tuberculosis (TB), a prehistoric disease, remains one of the top 10 causes of death and the leading cause from a single infectious agent, Mycobacterium tuberculosis, despite global efforts in disease control programs during the past 20 years [1]
Comprehensive comparative analysis of CYP139 P450s in 1111 mycobacterial species belonging to six different categories (Table S1) revealed that CYP139 P450s are present in 894 mycobacterial species belonging to three categories, namely the Mycobacterium tuberculosis complex (MTBC), M. avium complex (MAV) and non-tuberculosis mycobacteria (NTM) (Figure 1 and Table S2)
This study is an attempt to utilize the availability of quite a large number of mycobacterial species genome sequences and different bioinformatics tools to understand the role of the orphan CYP139 family in mycobacterial species
Summary
Tuberculosis (TB), a prehistoric disease, remains one of the top 10 causes of death and the leading cause from a single infectious agent, Mycobacterium tuberculosis, despite global efforts in disease control programs during the past 20 years [1]. TB is a global disease, found in every country in the world [1]. It became mankind’s oldest and worst enemy owing to its widespread nature across the world and developing resistance to known and available drugs [1]. After 21 years of M. tuberculosis genome sequencing [3], to date its physiology is poorly understood and many proteins remain orphans. P450s are well known for their role in essential cellular anabolic and catabolic processes
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