Cytochrome P450 Monooxygenase CYP139 Family Involved in the Synthesis of Secondary Metabolites in 824 Mycobacterial Species
Abstract
:1. Introduction
2. Results and Discussion
2.1. CYP139 P450s Are Present Only in Certain Mycobacterial Category Species
2.2. CYP139 P450 Family Ranked among Top 10 P450 Families
2.3. CYP139 Family Has Unique Amino Acid Patterns at CXG Motif
2.4. Most CYP139A P450s Are Part of Secondary Metabolite Biosynthetic Gene Clusters
2.5. CYP139A P450s Involved in the Synthesis of Secondary Metabolites in Mycobacterial Species
3. Materials and Methods
3.1. Mycobacterial Species and Genome Databases
3.2. Genome Data Mining and Annotation of CYP139 P450s
3.3. Phylogenetic Analysis of CYP139A P450s
3.4. Analysis of Homology and Amino Acid Conservation
3.5. Generation of EXXR and CXG Sequence Logo
3.6. Identification of CYP139 P450 Secondary Metabolite BGCs
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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P450 Family | Number of Member P450s | Kingdom | PROMALS3D Conservation Index | Rank (Highest to Lowest Conservation) | ||||
---|---|---|---|---|---|---|---|---|
5 | 6 | 7 | 8 | 9 | ||||
CYP141 | 29 | Bacteria | 0 | 0 | 0 | 0 | 389 | 1 |
CYP51 | 50 | Bacteria | 11 | 102 | 0 | 0 | 264 | 2 |
CYP137 | 38 | Bacteria | 145 | 0 | 0 | 0 | 251 | 3 |
CYP121 | 34 | Bacteria | 0 | 0 | 0 | 0 | 233 | 4 |
CYP132 | 39 | Bacteria | 175 | 0 | 0 | 0 | 217 | 5 |
CYP5619 | 23 | Stramenopila (oomycetes) | 118 | 38 | 170 | 0 | 199 | 6 |
CYP124 | 71 | Bacteria | 52 | 35 | 59 | 0 | 170 | 7 |
CYP139 | 894 | Bacteria | 0 | 127 | 0 | 0 | 165 | 8 (formerly 12) |
CYP188 | 67 | Bacteria | 62 | 0 | 100 | 0 | 141 | 9 |
CYP123 | 74 | Bacteria | 62 | 0 | 82 | 0 | 137 | 10 |
Gene Cluster | Function | Reference |
---|---|---|
ML-449 | Macrolactam antifungal-antibiotic production. | [41] |
MAR/MAP | Synthesis of methylated alkyl-resorcinol and methylated acyl-phloroglucinol products found to be part of cell envelope in M. marinum. | [30] |
Nystatin | Polyene antifungal antibiotic. | [42] |
Jerangolid | Antifungal polyketide. | [43] |
Piericidin A1 | A member of α-pyridone antibiotics, exhibits various biological activities such as antimicrobial, antifungal, and antitumour properties and possesses potent respiration-inhibitory activity against insects owing to its competitive binding capacity to mitochondrial complex I. | [44] |
Streptomycin | Antibiotic used to treat bacterial infections, including tuberculosis. | [45] |
Nanchangmycin | A polyether ionophore antibiotic produced by Streptomyces nanchangensis NS3226 that has insecticidal and in vitro antibacterial properties. Nanchangmycin exhibits antiviral properties against the Zika virus. | [46,47,48] |
Neoaureothin | Neoaureothin is an unusual chain-extended analog of aureothin. It was first reported as a co-metabolite of neoantimycin in Streptomyces orinoci. It has been reported to have anti-HIV and antifungal activity. | [49] |
Akaeolide | A carbocyclic polyketide with moderate antimicrobial activity and cytotoxicity to rat fibroblasts. | [31] |
Kendomycin | Macrolide antibiotic with antibacterial activity. | [50] |
ECO-02301 | Antifungal agent. | [51] |
Tiacumicin B | Macrolide antibiotic, which is used for the treatment of Clostridium difficile infections. | [52,53] |
Apoptolidin | Macrolide antibiotic well known as apoptosis inducer and inhibitor of F0F1-ATPase. It is a promising new therapeutic lead that exhibits remarkable selectivity against cancer cells relative to normal cells. | [54,55,56] |
Abyssomicin | A novel spirotetronate polyketide Class I antimicrobial. The biological activity of abyssomicins includes their antimicrobial activity against Gram-positive bacteria and mycobacteria, antitumour properties, latent HIV reactivator, anti-HIV and HIV replication inducer properties | [57] |
JBIR-100 | A new 16-membered tetraene macrolide from the Streptomyces species. Its structure is identical to TS155-2, which is an inhibitor of the thrombin-induced calcium influx. It exhibits cytotoxic and V-ATPases inhibition activities. V-ATPases are ubiquitous proton pumps present in the endomembrane system of all eukaryotic cells and in the plasma membranes of many animal cells that have been correlated with an increasing number of diseases such as osteopetrosis, male infertility and renal acidosis. | [32,33] |
Micromonolactam | A new polyene macrolactam antibiotic | [58] |
Lorneic acid A | It has a fatty acid-like structure in which a benzene ring is embedded. It inhibits phosphodiesterases (PDE) with selectivity toward PDE5, thus, blocking the degradation of cGMP and having a possible linkage to pulmonary hypertension | [34] |
Leucanicidin | A potent nematocide and insecticide macrolide | [59] |
Oligomycin | A natural antibiotic that inhibits mitochondrial ATP synthase, thus affecting the electron transport chain. | [60] |
Spirangien | Highly cytotoxic and antifungal spiroketal | [61] |
Stenothricin | A peptide antibiotic inhibiting bacterial cell wall synthesis | [62] |
Borrelidin | A small molecule nitrile-containing macrolide, which is an inhibitor of bacterial and eukaryal threonyl-tRNA synthetase. It exhibits among others antibacterial and anti-angiogenesis activities, suppresses growth and induces apoptosis in malignant acute lymphoblastic leukemia cells. | [63,64] |
FD-891 | Profoundly blocked both perforin- and FasL-dependent cytotoxicity by cytotoxic T lymphocytes—immunosuppressive. | [65] |
FR-008 | Macrolide antibiotic with antifungal activity. | [66] |
Meridamycin | A 27-membered macrolide that acts as non-immunosuppressive FK506-binding proteins (FKBP12) ligand. | [35] |
Ambruticin | Antifungal polyketide | [67] |
Nigericin | Nigericin acts as an H+, K+, Pb2+ ionophore. Most commonly it is an antiporter of H+ and K+. In the past nigericin was used as an antibiotic active against Gram-positive bacteria. It inhibits Golgi functions in eukaryotic cells. Its ability to induce K+ efflux also makes it a potent activator of the NLRP3 inflammasome. | [37,38,39] |
Mycolactone | Lipid-like toxin with cytotoxic, immunosuppressive and tissue necrosis activity. It plays a key role in the development of Buruli ulcer by M. ulcerans. | [40] |
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Syed, P.R.; Chen, W.; Nelson, D.R.; Kappo, A.P.; Yu, J.-H.; Karpoormath, R.; Syed, K. Cytochrome P450 Monooxygenase CYP139 Family Involved in the Synthesis of Secondary Metabolites in 824 Mycobacterial Species. Int. J. Mol. Sci. 2019, 20, 2690. https://doi.org/10.3390/ijms20112690
Syed PR, Chen W, Nelson DR, Kappo AP, Yu J-H, Karpoormath R, Syed K. Cytochrome P450 Monooxygenase CYP139 Family Involved in the Synthesis of Secondary Metabolites in 824 Mycobacterial Species. International Journal of Molecular Sciences. 2019; 20(11):2690. https://doi.org/10.3390/ijms20112690
Chicago/Turabian StyleSyed, Puleng Rosinah, Wanping Chen, David R. Nelson, Abidemi Paul Kappo, Jae-Hyuk Yu, Rajshekhar Karpoormath, and Khajamohiddin Syed. 2019. "Cytochrome P450 Monooxygenase CYP139 Family Involved in the Synthesis of Secondary Metabolites in 824 Mycobacterial Species" International Journal of Molecular Sciences 20, no. 11: 2690. https://doi.org/10.3390/ijms20112690