vestichИзвестия Национальной академии наук Беларуси. Серия химических наукProceedings of the National Academy of Sciences of Belarus, Chemical Series1561-83312524-2342The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8331-2024-60-3-235-245vestich-899Research ArticleБИООРГАНИЧЕСКАЯ ХИМИЯBIOORGANIC CHEMISTRYЛиганд-связывающие характеристики CYP51 Mycobacterium tuberculosis в отношении стероидных соединений из морских организмовLigand-binding characteristics of CYP51 Mycobacterium tuberculosis in relation to marine steroid compoundsКарпутьЕ. Ю.KarputsA. I.

Карпуть Елена Юрьевна – младший научный сотрудник

ул. Академика Купревича, 5/2, 220084, Минск

Karputs Alena I. – Junior Researcher

5/2, Akademic Kuprevich Str., 220084, Minsk

alena.karputs@gmail.comКапустинаИ. И.KapustinaI. I.

Капустина Ирина Ивановна – кандидат химическихнаук, научный сотрудник

(пр-т 100 лет Владивостоку, 159, 690022, Владивосток

Kapustina Irina I. – Ph. D. (Chemistry), Researcher

159, pr. 100-let Vladivostoku, 690022, Vladivostok

ikapust@rambler.ruТабакмахерК. М.TabakmakherK. M.

Табакмахер Ксения Михайловна – кандидат химических наук, научный сотрудник

пр-т 100 лет Владивостоку, 159, 690022, Владивосток

Tabakmakher Ksenia M. – Ph. D. (Chemistry), Researcher

159, pr. 100-let Vladivostoku, 690022, Vladivostok 

tabakmakher_km@piboc.dvo.ruМакарьеваТ. Н.MakarievaT. N.

Макарьева Татьяна Николаевна – доктор химическихнаук, главный научный сотрудник

пр-т 100 лет Владивостоку, 159, 690022, Владивосток

Makarieva Tatyana N. – Dr. Sc. (Chemistry), Chief Researcher

159, pr. 100-let Vladivostoku, 690022, Vladivostok

makarieva@piboc.dvo.ruКичаА. А.KichaA. A.

Кича Алла Анатольевна – доктор химических наук,ведущий научный сотрудник

пр-т 100 лет Владивостоку, 159, 690022, Владивосток

Kicha Alla A. – Dr. Sc. (Chemistry), Leading Researcher

159, pr. 100-let Vladivostoku, 690022, Vladivostok

kicha@piboc.dvo.ruИванчинаН. В.IvanchinaN. V.

Иванчина Наталья Владимировна – кандидат химических наук, заведующий лаборатории

пр-т 100 лет Владивостоку, 159, 690022, Владивосток

Ivanchina Natalia V. – Ph. D. (Chemistry), Head of thelaboratory

159, pr. 100-let Vladivostoku, 690022, Vladivostok

ivanchina@piboc.dvo.ruДмитренокП. С.DmitrenokP. S.

Дмитренок Павел Сергеевич – доктор химическихнаук, директор

пр-т 100 лет Владивостоку, 159, 690022

Dmitrenok Pavel S. – Dr. Sc. (Chemistry), Director

159, pr. 100-let Vladivostoku, 690022, Vladivostok

paveldmt@piboc.dvo.ruКалужскийЛ. А.KaluzhskiyL. A.

Калужский Леонид Александрович – кандидат биологических наук, научный сотрудник

ул. Погодинская, д. 10, стр. 8, 119121, Москва

Kaluzhskiy Leonid A. – Ph. D. (Biology), Researcher

10, b. 8, Pogodinskaya str., 119121, Moscow

leonid.kaluzhskiy@ibmc.msk.ruГилепА. Н.GilepA. A.

Гилеп Андрей Александрович – кандидат химических наук, доцент, ведущий научный сотрудник

ул. Академика Купревича, 5/2, 220084

Gilep Andrei A. – Ph. D. (Chemistry), Associate Professor, Leading Researcher

5/2, Kuprevich Str., 220084, Minsk

Институт биоорганической химии Национальной академии наук БеларусиInstitute of Bioorganic Chemistry of the National Academy of Sciences of BelarusТихоокеанский институт биоорганической химии имени Г. Б. Елякова Дальневосточного отделения Российской академии наукG. B. Elyakov Pacific Institute of Bioorganic Chemistry FEB RASНаучно-исследовательский институт биомедицинской химии имени В. Н. ОреховичаInstitute of Biomedical ChemistryInstitute of Bioorganic Chemistry of the National Academy of Sciences of BelarusBelarus202404092024603235245Copyright © Карпуть Е.Ю., Капустина И.И., Табакмахер К.М., Макарьева Т.Н., Кича А.А., Иванчина Н.В., Дмитренок П.С., Калужский Л.А., Гилеп А.Н., 20242024Карпуть Е.Ю., Капустина И.И., Табакмахер К.М., Макарьева Т.Н., Кича А.А., Иванчина Н.В., Дмитренок П.С., Калужский Л.А., Гилеп А.Н.Karputs A.I., Kapustina I.I., Tabakmakher K.M., Makarieva T.N., Kicha A.A., Ivanchina N.V., Dmitrenok P.S., Kaluzhskiy L.A., Gilep A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestichem.belnauka.by/jour/article/view/899

Стероид-14α-деметилазы CYP51 – представители крупного суперсемейства ферментов цитохромов Р450, обнаруженные во всех царствах живых организмов и катализирующие реакцию 14α-деметилирования ряда природных стероидов, включая ланостерин, обтузифолиол и 24,25-дигидроланостерин. CYP51 являются важными компонентами цепи биосинтеза стероидов у эукариот и по этой причине представляют одну из основных мишеней противогрибковой терапии. Ген, гомологичный стероид-14α-деметилазе CYP51, также обнаружен в геноме Mycobacterium tuberculosis. При этом у M. tuberculosis отсутствует путь de novo биосинтеза стероидов. Консервативность CYP51 среди представителей рода Mycobacterium и колокализация в геноме с 3Fe-4S ферредоксином Rv0763c, который поддерживает его каталитическую активность in vitro, могут косвенно указывать на участие CYP51 в важном для микобактерий биохимическом процессе. С целью установления специфичности активного центра MTCYP51 в отношении различных соединений изопреноидной природы нами получен высокоочищенный белковый препарат MTCYP51 и с помощью методов спектрофотометрического титрования и поверхностного плазмонного резонанса проведены исследования взаимодействия MTCYP51 со стероидами из морских организмов, полученными в Тихоокеанском институте биоорганической химии Дальневосточного отделения Российской академии наук. Исследованные соединения представляют собой широкий набор эволюционно древних изопреноидов. Результаты показали, что MTCYP51 способен связывать в активном центре разнообразные по структуре производные стероидов. Проведенные исследования позволяют предположить биологическую роль MTCYP51 для патогенных микобактерий, заключающуюся в связывании и возможном метаболизме экзогенных биорегуляторных изопреноидов в условиях in vivo.

CYP51 steroid-14α-demethylases are members of a large superfamily of cytochrome P450 enzymes found in all kingdoms of living organisms, and catalyze the 14α-demethylation reaction of a number of natural steroids, including lanosterol, obtusifoliol, and 24,25-dihydrolanosterol. CYP51 are important components of the eukaryotic steroid biosynthetic chain, and thus represent one of the main targets for antifungal therapy. A 14α-demethylase CYP51 homologous gene has also been found in the genome of Mycobacterium tuberculosis. At the same time, M. tuberculosis lacks the de novo pathway for steroid biosynthesis. Conservation of CYP51 among the Mycobacterium genus and colocalization in the genome with 3Fe-4S ferredoxin Rv0763c, which maintains its catalytic activity in vitro, may indirectly indicate the involvement of MTCYP51 in a biochemical process important for mycobacteria. In order to characterize the specificity of the MTCYP51 active site to various compounds of isoprenoid nature, we obtained a highly purified MTCYP51 and, using spectrophotometric titration and surface plasmon resonance methods, studied the interaction of MTCYP51 with steroids from marine organisms obtained in the Pacific Institute of Bioorganic Chemistry of the Far Eastern Branch of the Russian Academy of Sciences. The investigated compounds represent a wide range of evolutionarily ancient isoprenoids. The results showed that MTCYP51 is able to bind structurally diverse steroid derivatives in the active site. The conducted studies suggest the biological role of MTCYP51 for pathogenic mycobacteria, which consists in the binding and possible metabolism of exogenous bioregulatory isoprenoids in vivo. 

стероид-14α-деметилазаизопреноидыцитохром Р450микобактериитуберкулезгетерологическая экспрессиявысокоэффективная жидкостная хроматографияSPR-анализспектрофотометрическое титрованиеsteroid-14α-demethylaseisoprenoidscytochrome P450mycobacteriatuberculosisheterological expressionhigh-performance liquid chromatographySPR-analysisspectrophotometric titrationReferencesGlobal Tuberculosis Report, 2022 / World Health Organization. – Geneva: World Health organization, 2022. – 68 p.World Health organization. Global tuberculosis report 2022. Geneva, 2022.Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence / S. T. Cole [et al.] // Nature. – 1998. – Vol. 393, № 6685. – P. 537–544. https://doi.org/10.1038/31159Cole, S. T., Brosch R., Parkhill J., Garnier T., Churcher C., Harris D. E., Gordon S. V. [et al.]. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature, 1998, vol. 393, no. 6685, pp. 537–544. https:// doi.org/10.1038/31159CYP51-like gene of Mycobacterium tuberculosis actually encodes a P450 similar to eukaryotic CYP51 / Y. Aoyama [et al.] // J. Biochem. – 1998. – Vol. 124, № 4. – P. 694–696. https://doi.org/10.1093/oxfordjournals.jbchem.a022167Aoyama Y., Horiuchi T., Gotoh O., Noshiro M., Yoshida Y. CYP51-like gene of Mycobacterium tuberculosis actually encodes a P450 similar to eukaryotic CYP51. Journal of Biochemistry, 1998, vol. 124, no. 4, pp. 694–696. https://doi.org/10.1093/oxfordjournals.jbchem.a022167Characterization and catalytic properties of the sterol 14alpha-demethylase from Mycobacterium tuberculosis / A. Bellamine [et al.] // Proc. Natl. Acad. Sci. USA. – 1999. – Vol. 96, № 16. – P. 8937–8942. https://doi.org/10.1073/pnas.96.16.8937Bellamine A., Mangla A. T., Nes W. D., Waterman M. R. Characterization and catalytic properties of the sterol 14alpha-demethylase from Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences USA, 1999, vol. 96, no. 16, pp. 8937–8942. https://doi.org/10.1073/pnas.96.16.8937Strushkevich, N. Structural basis of human CYP51 inhibition by antifungal azoles / N. Strushkevich, S.A. Usanov, H.-W. Park // J. Mol. Biol. – 2010. – Vol. 397, № 4. – P. 1067–1078. https://doi.org/10.1016/j.jmb.2010.01.075Strushkevich, N., Usanov S. A., Park H.-W. Structural basis of human CYP51 inhibition by antifungal azoles. Journal of Molecular Biology, 2010, vol. 397, no. 4, pp. 1067–1078. https://doi.org/10.1016/j.jmb.2010.01.075Lamb, D. C. The first virally encoded cytochrome p450 / D.C. Lamb [et al.] // J. Virol. – 2009. – Vol. 83, № 16. – P. 8266–8269. https://doi.org/10.1128/JVI.00289-09Lamb D. C., Lei L., Warrilow A. G. S., Lepesheva G. I., Mullins J. G. L., Waterman M. R., Kelly S. L. The first virally encoded cytochrome p450. Journal of Virology, 2009, vol. 83, no. 16, pp. 8266–8269. https://doi.org/10.1128/jvi.00289-09Comprehensive essentiality analysis of the Mycobacterium tuberculosis genome via saturating transposon mutagenesis / M. A. DeJesus [et al.] // mBio. – 2017. – Vol. 8, № 1. – P. 1–17. https://doi.org/10.1128/mBio.02133-16DeJesus M. A., Gerrick E. R., Xu W., Park S. W., Long J. E., Boutte C. C., Rubin E. J. [et al.]. Comprehensive essentiality analysis of the Mycobacterium tuberculosis genome via saturating transposon mutagenesis. mBio, 2017, vol. 8, no. 1, pp. 1–17. https://doi.org/10.1128/mBio.02133-16Transcriptional adaptation of drug-tolerant Mycobacterium tuberculosis in mice [Electronic Resource] / E. A. Wynn [et al.] // bioRxiv [Preprint]. – 2023, March 08. – Mode of access: https://www.biorxiv.org/content/10.1101/2023.03.06.531356v2. https://doi.org/10.1101/2023.03.06.531356Wynn E. A., Dide-Agossou C., Reichlen M., Rossmassler K., Mubarak R. A., Reid J. J., Tabor S. T. [et al.]. Transcriptional adaptation of drug-tolerant Mycobacterium tuberculosis in mice. bioRxiv [Preprint], 2023, March 08. Available at: https://www.biorxiv.org/content/10.1101/2023.03.06.531356v2. https://doi.org/10.1101/2023.03.06.531356Structural insights into 3Fe–4S ferredoxins diversity in M. tuberculosis highlighted by a first redox complex with P450 / A. Gilep [et al.] // Front. Mol. Biosci. – 2023. – Vol. 9. – P. 1–15. https://doi.org/10.3389/fmolb.2022.1100032Gilep A., Varaksa T., Bukhdruker S., Kavaleuski A., Ryzhykau Y., Smolskaya S., Sushko T. Structural insights into 3Fe–4S ferredoxins diversity in M. tuberculosis highlighted by a first redox complex with P450. Frontiers in Molecular Biosciences, 2023, vol. 9, pp. 1–15. https://doi.org/10.3389/fmolb.2022.1100032X-ray structure of 4, 4′-dihydroxybenzophenone mimicking sterol substrate in the active site of sterol 14α-demethylase (CYP51) / A. N. Eddine [et al.] // J. Biol. Chem. – 2008. – Vol. 283, № 22. – P. 15152–15159. https://doi.org/10.1074/jbc.M801145200Eddine A. N., Kries J. P., Podust M. V., Warrier T., Kaufmann S. H. E., Podust L. M. X-ray structure of 4, 4′-dihydroxybenzophenone mimicking sterol substrate in the active site of sterol 14α-demethylase (CYP51). Journal of Biological Chemistry, 2008, vol. 283, no. 22, pp. 15152–15159. https://doi.org/ 10.1074/jbc.M801145200Estriol bound and ligand-free structures of sterol 14alpha-demethylase / L. M. Podust [et al.] // Structure. – 2004. – Vol. 12, № 11. – P. 1937–1945. https://doi.org/10.1016/j.str.2004.08.009Podust L. M., Yermalitskaya L. V., Lepesheva G. I., Podust V. N., Dalmasso E. A., Waterman M. R. Estriol bound and ligand-free structures of sterol 14alpha-demethylase. Structure, 2004, vol. 12, no. 11, pp. 1937–1945. https://doi.org/10.1016/j. str.2004.08.009Human lanosterol 14-alpha demethylase (CYP51A1) Is a putative target for natural flavonoid luteolin 7, 3′-disulfate / L. Kaluzhskiy [et al.] // Molecules. – 2021. – Vol. 26, № 8. – P. 2237. https://doi.org/10.3390/molecules26082237Kaluzhskiy L., Ershov P., Yablokov E., Shkel T., Grabovec I., Mezentsev Y., Gnedenko O. [et al.]. Human lanosterol 14-alpha demethylase (CYP51A1) Is a putative target for natural flavonoid luteolin 7, 3′-disulfate. Molecules, 2021, vol. 26, no. 8, pp. 2237. https://doi.org/10.3390/molecules26082237CYP51 from Trypanosoma brucei is obtusifoliol-specific / G. I. Lepesheva [et al.] // Biochemistry. – 2004. – Vol. 43, № 33. – P. 10789–10799. https://doi.org/10.1021/bi048967tLepesheva G. I., Nes W. D., Zhou W., Hill G. C., Waterman M. R. CYP51 from Trypanosoma brucei is obtusifoliolspecific. Biochemistry, 2004, vol. 43, no. 33, pp. 10789–10799. https://doi.org/10.1021/bi048967tSchenkman, J. B. Spectral analyses of cytochromes P450 / J. B. Schenkman, I. Jansson // Methods Mol. Biol. – 2006. – Vol. 320. – P. 11–18. https://doi.org/10.1385/1-59259-998-2:11Schenkman J. B., Jansson I. Spectral analyses of cytochromes P450. Methods in molecular biology, 2006, vol. 320, pp. 11–18. https://doi.org/10.1385/1-59259-998-2:11The structure of Mycobacterium tuberculosis CYP125: molecular basis for cholesterol binding in a P450 needed for host infection / K. J. McLean [et al.] // J. Biol. Chem. – 2009. – Vol. 284, № 51. – P. 35524–35533. https://doi.org/10.1074/jbc.M109.032706McLean K. J., Lafite P., Levy C., Cheesman M. R., Mast N., Pikuleva I. A., Leys D., Munro A. W. The structure of Mycobacterium tuberculosis CYP125: molecular basis for cholesterol binding in a P450 needed for host infection. Journal of Biological Chemistry, 2009, vol. 284, no. 51, pp. 35524–35533. https://doi.org/10.1074/jbc.M109.032706Biosynthetic studies of marine lipids. 42. Biosynthesis of steroid and triterpenoid metabolites in the sea cucumber Eupentacta fraudatrix / T. N. Makarieva [et al.] // Steroids. – 1993. – Vol. 58, N 11. – P. 508–517. https://doi.org/10.1016/0039-128x(93)90026-jMakarieva T. N., Stonik V. A., Kapustina I. I., Boguslavsky V. M., Dmitrenoik A. S., Kalinin V. I., Cordeiro M. L., Djerassi C. Biosynthetic studies of marine lipids. 42. Biosynthesis of steroid and triterpenoid metabolites in the sea cucumber Eupentacta fraudatrix. Steroids, 1993, vol. 58, no. 11, pp. 508–517. https://doi.org/10.1016/0039-128x(93)90026-jCyclic steroid glycosides from the starfish Echinaster luzonicus: Structures and immunomodulatory activities / A. A. Kicha [et al.] // J. Nat. Prod. – 2015. – Vol. 78, N 6. – P. 1397–1405. https://doi.org/10.1021/acs.jnatprod.5b00332Kicha A. A., Kalinovsky A. I., Malyarenko T. V., Ivanchina N. V., Dmitrenok P. S., Menchinskaya E. S., Yurchenko E. A. [et al.]. Cyclic steroid glycosides from the starfish Echinaster luzonicus: Structures and immunomodulatory activities. Journal of Natural Products, 2015, vol. 78, no. 6, pp. 1397–1405. https://doi.org/10.1021/acs.jnatprod.5b00332Six new polyhydroxysteroidal glycosides, anthenosides S1–S6, from the starfish Anthenea sibogae / A. A. Kicha [et al.] // Chem. Biodiver. – 2018. – Vol. 15, № 3. – P. 1–12. https://doi.org/10.1002/cbdv.201700553Kicha A. A., Ha D. T., Ivanchina N. V., Malyarenko T. V., Kalinovsky A. I., Dmitrenok P. S., Ermakova S. P. Six new polyhydroxysteroidal glycosides, anthenosides S1–S6, from the starfish Anthenea sibogae. Chemistry & Biodiversity, 2018, vol. 15, no. 3, pp. 1–12. https://doi.org/10.1002/cbdv.201700553Unusual polyhydroxylated steroids from the starfish Anthenoides laevigatus, collected of the coastal waters of Vietnam / A. A. Kicha [et al.] // Molecules. – 2020. – Vol. 25, № 6. – P. 1–12. https://doi.org/10.3390/molecules25061440Kicha A. A., Ha D. T., Malyarenko T. V., Kalinovsky A. I., Popov R. S., Malyarenko O. S., Thuy Tran T. T. Unusual polyhydroxylated steroids from the starfish Anthenoides laevigatus, collected of the coastal waters of Vietnam. Molecules, 2020, vol. 25, no. 6, pp. 1–12. https://doi.org/10.3390/molecules25061440Granulatosides D, E and other polar steroid compounds from the starfish Choriaster granulatus. Their immunomodulatory activity and cytotoxicity / N. V. Ivanchina [et al.] // Nat. Prod. Res. – 2019. – Vol. 33, № 18. – P. 2623–2630. https://doi.org/10.1080/14786419.2018.1463223Ivanchina N. V., Kicha A. A., Malyarenko T. V., Ermolaeva S. D., Yurchenko E. A., E. A. Pislyagin, Minh C. V., Dmitrenok P. S. Granulatosides D, E and other polar steroid compounds from the starfish Choriaster granulatus. Their immunomodulatory activity and cytotoxicity. Natural Product Research, 2019, vol. 33, no. 18, pp. 2623–2630. https://doi.org/ 10.1080/14786419.2018.1463223Highly hydroxylated steroids of the starfish Archaster typicus from the Vietnamese waters / N. V. Ivanchina [et al.] // Steroids. – 2010. – Vol. 75, № 12. – P. 897–904. https://doi.org/10.1016/j.steroids.2010.05.012Ivanchina N. V., Kicha A. A., Huong T. T. T., Kalinovsky A. I., Dmitrenok P. S., Agafonova I. G., Long P. Q., Stonik V. A. Steroids, 2010, vol. 75, no. 12, pp. 897–904. https://doi.org/10.1016/j.steroids.2010.05.012Tabakmakher, K. M. New trisulfated steroids from the Vietnamese marine sponge Halichondria vansoesti and their PSA expression and glucose uptake inhibitory activities / K. M. Tabakmakher [et al.] // Mar. Drugs. – 2019. – Vol. 17, № 8. – P. 445. https://doi.org/10.3390/md17080445Tabakmakher K. M., Makarieva T. N., Denisenko V. A., Popov R. S., Dmitrenok P. S., Dyshlovoy S. A., Grebnev B. B. New trisulfated steroids from the Vietnamese marine sponge Halichondria vansoesti and their PSA expression and glucose uptake inhibitory activities. Marine Drugs, 2019, vol. 17, no. 8, pp. 455. https://doi.org/10.3390/md17080445Biosensor‐surface plasmon resonance methods for quantitative analysis of biomolecular interactions / F. A. Tanious [et al.] // Methods Cell Biol. – 2008. – Vol. 84. – P. 53–77. https://doi.org/10.1016/S0091-679X(07)84003-9Tanious F. A., Nguyen B., Wilson W. D. Biosensor‐surface plasmon resonance methods for quantitative analysis of biomolecular interactions. Methods in Cell Biology, 2008, vol. 84, pp. 53–77. https://doi.org/10.1016/S0091-679X(07)84003-9Lipschultz, C. A. Experimental design for analysis of complex kinetics using surface plasmon resonance / C. A. Lipschultz, Y. Li, S. Smith-Gill // Methods. – 2000. – Vol. 20, № 3. – P. 310–318. https://doi.org/10.1006/meth.1999.0924Lipschultz C. A., Li Y., Smith-Gill S. Experimental design for analysis of complex kinetics using surface plasmon resonance. Methods, 2000, vol. 20, no. 3, pp. 310–318. https://doi.org/10.1006/meth.1999.0924Schenkman, J. B. Substrate interaction with cytochrome P-450 / J. B. Schenkman, S. G. Sligar, D. L. Cinti // Pharmacol. Ther. – 1981. – Vol. 12, № 1. – P. 43–71. https://doi.org/10.1016/0163-7258(81)90075-9Schenkman J. B., Sligar S. G., Cinti D. L. Substrate interaction with cytochrome P-450. Pharmacology & Therapeutics, 1981, vol. 12, no. 1, pp. 43–71. https://doi.org/10.1016/0163-7258(81)90075-9Podust, L. M. Crystal structure of cytochrome P450 14α-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors / L. M. Podust, T. L. Poulos, M. R. Waterman // Proc. Natl. Acad. Sci. USA. – 2001. – Vol. 98, № 6. – P. 3068–3073. https://doi.org/10.1073/pnas.061562898Podust L. M., Poulos T. L., Waterman M. R. Crystal structure of cytochrome P450 14α-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors. Proceedings of the National Academy of Sciences of the United States of America, 2001, vol. 98, no. 6, pp. 3068–3073. https://doi.org/10.1073/pnas.061562898Metabolic fate of human immunoactive sterols in Mycobacterium tuberculosis / T. Varaksa [et al.] // J. Mol. Biol. – 2021. – Vol. 433, № 4. – P. 1–16. https://doi.org/10.1016/j.jmb.2020.166763Varaksa T., Bukhdruker S., Grabovec I., Marin E., Kavaleuski A., Gusach A., Kovalev K. [et al.]. Metabolic fate of human immunoactive sterols in Mycobacterium tuberculosis. Journal of Molecular Biology, 2021, vol. 433, no. 4, pp. 1–16. https://doi.org/ 10.1016/j.jmb.2020.166763Identification of Mycobacterium tuberculosis enzyme involved in vitamin D and 7-dehydrocholesterol metabolism / A. V. Vasilevskaya [et al.] // J. Steroid Biochem. Mol. Biol. – 2017. – Vol. 169. – P. 202–209. https://doi.org/10.1016/j.jsbmb.2016.05.021Vasilevskaya A. V., Yantsevich A. V., Sergeev G. V., Lemish A. P., Usanov S. A., Gilep A. A. Identification of Mycobacterium tuberculosis enzyme involved in vitamin D and 7-dehydrocholesterol metabolism. Journal of Steroid Biochemistry and Molecular Biology, 2017, vol. 169, pp. 202–209. https://doi.org/10.1016/j.jsbmb.2016.05.02

The authors declare that there are no conflicts of interest present.