vestibИзвестия Национальной академии наук Беларуси. Серия биологических наукProceedings of the National Academy of Sciences of Belarus, Biological Series1029-89402524-230XThe Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1029-8940-2025-70-4-321-330vestib-989Research ArticleСтатьиФерментативный однореакторный препаративный синтез 6-тио-2′-дезоксигуанозинаOne-pot enzymatic preparative synthesis of 6-thio-2′-deoxyguanosineБиричевскаяЛ. Л.BirуcheuskayaL. L.

Биричевская Лариса Леонидовна – канд. биол. наук, доцент, вед. науч. сотрудник.

ул. Академика Купревича, 2, 220084, Минск

Larysa L. Birycheuskaya – Ph. D. (Biol.), Associate Professor, Leading Researcher, Institute of Microbiology of the National Academy of Sciences of Belarus.

2, Academician Kuprevich Str., 220084, Minsk

larbir@mail.ruДайнекоА. В.DainekaH. V.

Дайнеко Анна Васильевна – мл. науч. сотрудник.

ул. Академика Купревича, 2, 220084, Минск

Hanna V. Daineka – Junior Researcher, Institute of Microbiology of the National Academy of Sciences of Belarus.

2, Academician Kuprevich Str., 220084, Minsk

daineko1999@list.ruЩеколоваА. С.ShchokalavaN. S.

Щеколова Анастасия Сергеевна – канд. биол. наук, ст. науч. сотрудник.

ул. Академика Купревича, 2, 220084, Минск

Nastassia S. Shchokalava – Ph. D. (Biol.), Senior Researcher, Institute of Microbiology of the National Academy of Sciences of Belarus.

2, Academician Kuprevich Str., 220084, Minsk

nastindeathnote@gmail.comhttps://orcid.org/0000-0003-2401-2586ЗинченкоА. И.ZinchenkoA. I.

Зинченко Анатолий Иванович – член-корреспондент, д-р биол. наук, профессор, заведующий лабораторией.

ул. Академика Купревича, 2, 220084, Минск

Anatoli I. Zinchenko – Corresponding Member, D. Sc. (Biol.), Professor, Head of the Laboratory, Institute of Microbiology of the National Academy of Sciences of Belarus.

2, Academician Kuprevich Str., 220084, Minsk

zinch@mbio.bas-net.byИнститут микробиологии Национальной академии наук БеларусиInstitute of Microbiology of the National Academy of Sciences of Belarus202507112025704321330Copyright © Биричевская Л.Л., Дайнеко А.В., Щеколова А.С., Зинченко А.И., 20252025Биричевская Л.Л., Дайнеко А.В., Щеколова А.С., Зинченко А.И.Birуcheuskaya L.L., Daineka H.V., Shchokalava N.S., Zinchenko A.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestibio.belnauka.by/jour/article/view/989

Разработан усовершенствованный биотехнологический способ получения 6-тио-2′-дезоксигуанозина – модифицированного нуклеозида, проявляющего уникально широкий спектр противоопухолевой активности. Препаративный однореакторный способ включает инкубирование при температуре 45 ℃ 6-тиогуанина и 2′-дезокситимидина в фосфатном буфере в присутствии рекомбинантных тимидинфосфорилазы и пуриннуклеозидфосфорилазы Escherichia coli и отличается от известного способа-аналога тем, что 2′-дезокситимидин и 6-тиогуанин вносят в реакционную смесь в количествах, намного превышающих их водорастворимость. Использование предлагаемого способа получения 6-тио-2′-дезоксигуанозина обеспечивает по сравнению с известным способом-прототипом увеличение выхода целевого продукта в расчете на исходный 2′-дезокситимидин с 14,6 до 33,5 % и повышение волюметрического выхода целевого продукта с 4,13 до 75,8 г/л реакционной смеси. Это существенно повышает эффективность использования единицы объема биореактора. Предлагаемый метод высокотехнологичен и может быть успешно применен в условиях производства.

An improved biotechnological method for producing 6-thio-2′-deoxyguanosine, a modified nucleoside exhibiting a uniquely broad spectrum of antitumor activity, has been developed. The one-pot preparative method involves incubation of 6-thioguanine and 2′-deoxythymidine at 45 °C in phosphate buffer in the presence of recombinant Escherichia coli thymidine phosphorylase and purine nucleoside phosphorylase. This method is distinct from the known analogue method in that 2′-deoxythymidine and 6-thioguanine are added to the reaction mixture in amounts that far exceed their water solubility. Utilizing the disclosed method of producing 6-thio-2′-deoxyguanosine increases yield of the end product based on the starting 2′-deoxythymidine from 14.6 to 33.5 % compared to the known prototype method and raises volumetric yield of the end product from 4.13 to 75.8 g/l of the reaction mixture. This significantly improves the efficiency of using a unit volume of the bioreactor. The proposed technology is high-tech and can be successfully applied under largescale production conditions.

6-тио-2′-дезоксигуанозинрекомбинантная тимидинфосфорилазарекомбинантная пуриннуклеозидфосфорилазабиокатализ6-тиогуанин2′-дезокситимидин6-thio-2′-deoxyguanosinerecombinant thymidine phosphorylaserecombinant purine nucleoside phosphorylasebiocatalysis6-thioguanine2′-deoxythymidineАвторы выражают благодарность за помощь в расшифровке спектра ЯМР профессору Е.И. Квасюку (МГЭИ им. А.Д. Сахарова БГУ), а также С.М. Грязнову за любезно предоставленный для работы реагент 6ТГ.The authors express their gratitude to Professor E. Kvasyuk (International Sakharov Environmental Institute of Belarusian State University) for assistance in decoding the NMR spectrum, and Dr. S. Gryaznov (MAIA Biotechnology, USA) for the 6TG reagent kindly provided for the work.ReferencesAdvances in the development of nucleoside and nucleotide analogues for cancer and viral diseases / L. P. Jordheim, D. Durantel, F. Zoulim, C. Dumontet // Nature Reviews. 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The authors declare that there are no conflicts of interest present.