nbsprotВестник войск РХБ защитыJournal of NBC Protection Corps2587-57283034-279127 Научный центр10.35825/2587-5728-2022-6-4-342-354dmkjoenbsprot-34Research ArticleХИМИЧЕСКАЯ БЕЗОПАСНОСТЬ И ЗАЩИТА ОТ ХИМИЧЕСКОГО ТЕРРОРИЗМАCHEMICAL SECURITY AND PROTECTION AGAINST CHEMICAL TERRORISMНовые ферментные мишени для фосфорорганических соединенийNew Enzymatic Targets for Organophosphorus CompoundsЕфременкоЕ. Н.EfremenkoE. N.

Ефременко Елена Николаевна. Зав. лабораторией, доктор биол. наук, профессор, заведующий лабораторией экобиокатализа, выполняющей госзадание.

119991, г. Москва, Ленинские горы, д. 1, стр. 3 

Elena Nikolayevna Efremenko. Chief of the laboratory of ecobiocatalysis. Doctor of Biological Sciences, Professor. Carrying out the state task.

Lenin Hills 1-3, Moscow 119991

elena_efremenko@list.ruАсланлыА. Г.AslanliA. G.

Асланлы Айсель Гюльхан. Научный сотрудник, канд. хим. наук, сотрудник лаборатории экобиокатализа, выполняющей госзадание.

119991, г. Москва, Ленинские горы, д. 1, стр. 3 

Ajsel' Gjul'han Aslanly. Researcher. Candidate of Chemical Sciences. Employee of the laboratory of ecobiocatalysis, performing a state assignment.

Lenin Hills 1-3, Moscow 119991

elena_efremenko@list.ruЛягинИ. В.LyaginI. V.

Лягин Илья Владимирович. Старший научный сотрудник, канд. хим. наук, сотрудник лаборатории экобиокатализа, выполняющей госзадание.  

119991, г. Москва, Ленинские горы, д. 1, стр. 3

Ilya Vladimirovich Lyagin. Senior Researcher. Candidate of Chemical Sciences. Employee of the laboratory of ecobiocatalysis, performing a state assignment.

Lenin Hills 1-3, Moscow 119991

elena_efremenko@list.ruМосковский государственный университет имени М.В. Ломоносова, химический факультетРоссияLomonosov Moscow State University, Faculty of ChemistryRussian Federation20221605202364342354Copyright © Ефременко Е.Н., Асланлы А.Г., Лягин И.В., 20232023Ефременко Е.Н., Асланлы А.Г., Лягин И.В.Efremenko E.N., Aslanli A.G., Lyagin I.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nbsprot.ru/jour/article/view/34

Декарбоксилаза ароматических аминокислот (ДАА), гистидиндекарбоксилаза (ГД) и глутаматдекарбоксилазы (ГлД) с разной молекулярной массой катализируют наиболее важные реакции биосинтеза нейротрансмиттеров и нейромодуляторов. Пиридоксальфосфат, который служит для этих ферментов кофактором, является фосфорорганическим соединением (ФОС), имеющим структуру, сходную с такими высокотоксичными отравляющими веществами (ОВ), как зарин, зоман, Vx, вещество типа Vx, табун и так называемыми «Новичками» (А230, А232, А234), а также с пестицидами, широко применяемыми в сельском хозяйстве (хлорпирифосом, малатионом, глифосатом, мипафоксом, диазиноном, параоксоном), исходя из их ингибирующего воздействия на холинэстеразы (ХЭ). Цель работы – с помощью методов компьютерного моделирования оценить возможность связывания различных ФОС с каталитическими центрами указанных ферментов вместо кофактора, а также аналогичные взаимодействия декарбоксилаз (ДК) с ФОС, когда активные центры ДК уже содержат встроенный кофактор. Молекулярный докинг показал, что целый ряд из указанных ФОС может конкурировать с кофактором за связывание с активными центрами ДК, причем все исследованные ФОС (пестициды и ОВ) создают препятствия для встраивания кофактора в активный центр ДАА и ГД. Подобные взаимодействия будут приводить к снижению уровня образования продуктов соответствующих каталитических реакций (дофамина, серотонина, фенилэтиламина, серотонина, γ-аминомасляной кислоты) и проявлению ими своих физиологических функций. Установлено, что при наличии кофактора в активном центре исследованных ДК, взаимодействие ряда ФОС с поверхностью этих ферментов возле активного центра усиливается и превышает силу взаимодействия этих же ферментов с их типичными субстратами. При этом максимальное взаимодействие, которое может приводить к существенной инактивации всех исследованных ДК, было выявлено для пестицидов, тогда как для ОВ эффект от их присутствия был ниже. Один из высоких уровней возможного влияния на активность ДК был выявлен для хлорпирифоса и диазинона. Суммарно, для ДК более опасными веществами с высокой потенциальной нейротоксичностью оказались вовсе не ОВ, включая «Новички», а именно пестициды, которые по их известному воздействию на ХЭ, считаются малотоксичными ФОС. Проведенные новые теоретические исследования свидетельствуют о том, что, во-первых, требуются прямые экспериментальные исследования, которые подтвердят произведенные биоинформацинные расчеты; во-вторых, необходим пересмотр давно существующих подходов к оценке нейротоксичности различных ФОС, основанных преимущественно на использовании ХЭ для этих целей; в-третьих, возможно следует сформулировать задачи по разработке и применению новых систем определения потенциально нейротоксичных веществ, действие которых будет основано на применении разных ДК; в четвертых, изучить возможность применения ДК в качестве основы для разработки новых каталитических ферментных детоксификаторов (антидотов) и регенераторов ЦНС.

It is known that several decarboxylases (aromatic amino acid decarboxylase (AAD), histidine decarboxylase (HD) and glutamate decarboxylase (GD) with different molecular weights catalyze the most important reactions of neurotransmitter and neuromodulator biosynthesis. Pyridoxal phosphate, which serves as a cofactor for these enzymes, is one of organophosphorus compounds (OPC) having a structure similar to highly toxic substances such as warfare agents (WA) sarin, soman, Vx, a substance of type Vx, tabun and the so-called «Novichoks» (A230, A232, A234), as well as pesticides, widely used in agriculture (chlorpyrifos, malathion, glyphosate, mipafox, diazinon, paraoxon), based on their inhibitory effect on cholinesterases (ChE). The purpose of this work was to use computer modeling methods to evaluate the possible binding of various OPC to the catalytic centers of these enzymes instead of a cofactor, as well as similar interactions of decarboxylases (DC) with OPC when the active centers of DC already contain a built-in cofactor. Molecular docking has shown that a number of these OPC can compete with the cofactor for binding to the active centers of DC, and absolutely all the studied OPC (pesticides and WA) create obstacles to embedding the cofactor in the active center of AAD and HD. Such interactions will lead to a decrease in the level of formation of products of the corresponding catalytic reactions (dopamine, serotonin, phenylethylamine, serotonin, γ-aminobutyric acid) and the manifestation of their physiological functions. It was found that in the presence of a cofactor in the active center of the studied DC, the interaction of a number of OPC with the surface of these enzymes near the active center increases and exceeds the strength of the interaction of same enzymes with their typical substrates. At the same time, the maximum interaction that can lead to a significant inactivation of all the studied DC was revealed for the pesticides, while the effect of their presence was lower for WA. One of the highest levels of possible influence on the activity of DC was revealed for chlorpyrifos and diazinon. In total, for DC, the more dangerous substances with high potential neurotoxicity turned out to be not WA at all, including «Novichoks», namely pesticides, which, according to their known effect on ChE, are considered as low-toxic OPC. The conducted new theoretical studies indicate that, firstly, direct experimental studies are required that will confirm the bioinformatics calculations made; secondly, a revision of long-standing approaches to assessing the neurotoxicity of various OPC, based mainly on the use of ChE for these purposes, is necessary; thirdly, it may be necessary to formulate tasks for the development and the use of new systems for the determination of potentially neurotoxic substances, the effect of which will be based on the use of different DC; fourth, to study the possible using DC as a basis for the development of new catalytic enzymatic detoxifiers (antidotes) and CNS regenerators.

фосфорорганические соединенияотравляющие веществапестицидыингибиторыдекарбоксилазыкомпьютерное моделированиепиридоксальфосфатнейродегенеративные заболеванияхимическая безопасностьchemical safetycomputer modelingdecarboxylasesinhibitorsneurodegenerative diseasesorganophosphorus compoundspesticidespyridoxal phosphatewarfare agentsРабота подготовлена при выполнении Госзадания МГУ имени М.В. Ломоносова №121041500039-8.The work was prepared in the performance of the State Assignment of Lomonosov Moscow State University No. 121041500039-8ReferencesФосфорорганические нейротоксины / Под ред. Варфоломеева С.Д., Ефременко Е.Н. М.: РИОР, 2020. 380 с. https://doi.org/10.29039/02026-5Organophosphorus neurotoxins / Eds. Varfolomeev S.D., Efremenko E.N. 1st ed.; Moscow: RIOR, 2020. 380 p. https://doi.org/10.29039/02026-5 (in Russian).Mukherjee S., Gupta R.D. Organophosphorus nerve agents: types, toxicity, and treatments // J. Toxicology. 2020. Article ID 3007984. https://doi.org/10.1155/2020/3007984Mukherjee S., Gupta R.D. Organophosphorus nerve agents: types, toxicity, and treatments // J. Toxicology. 2020. Article ID 3007984. https://doi.org/10.1155/2020/3007984Лягин И.В., Ефременко Е.Н. Ферменты и их формы, используемые для обнаружения фосфорорганических соединений // Вестник войск РХБ защиты. 2021. Т. 5, № 1. С. 22–41. https://doi.org/10.35825/2587-5728-2021-5-1-22-41Lyagin I.V., Efremenko E.N. Enzymes and their forms used in detection of organophosphorus compounds // Journal of NBC Protection Corps. 2021. V. 5. № 1. P. 22–41. https://doi.org/10.35825/2587-5728-2021-5-1-22-41 (in Russian).Greer J.B., Magnuson J.T., Hester K. et al. Effects of chlorpyrifos on cholinesterase and serine lipase activities and lipid metabolism in brains of rainbow trout (Oncorhynchus mykiss) // Toxicol. Sci. 2019. V. 172. P. 146–154. https://doi.org/10.1093/toxsci/kfz167Greer J.B., Magnuson J.T., Hester K. et al. Effects of chlorpyrifos on cholinesterase and serine lipase activities and lipid metabolism in brains of rainbow trout (Oncorhynchus mykiss) // Toxicol. Sci. 2019. V. 172. P. 146–154. https://doi.org/10.1093/toxsci/kfz167Liu L., Koo Y., Akwitti C. et al. Threedimensional (3D) brain microphysiological system for organophosphates and neurochemical agent toxicity screening // PLoS ONE. 2019. V. 14. P. e0224657. https://doi.org/10.1371/journal.pone.0224657Liu L., Koo Y., Akwitti C. et al. Threedimensional (3D) brain microphysiological system for organophosphates and neurochemical agent toxicity screening // PLoS ONE. 2019. V. 14. P. e0224657. https://doi.org/10.1371/journal.pone.0224657Brenet A., Somkhit J., Hassan-Abdi R. et al. Organophosphorus diisopropylfluorophosphate (DFP) intoxication in zebrafish larvae causes behavioral defects, neuronal hyperexcitation and neuronal death // Sci. Rep. 2020. V. 10. P. e19228. https://doi.org/10.1038/s41598-020-76056-8Brenet A., Somkhit J., Hassan-Abdi R. et al. Organophosphorus diisopropylfluorophosphate (DFP) intoxication in zebrafish larvae causes behavioral defects, neuronal hyperexcitation and neuronal death // Sci. Rep. 2020. V. 10. P. e19228. https://doi.org/10.1038/s41598-020-76056-8Hogberg H.T., de Cássia da Silveira E Sá R., Kleensang A. et al. Organophosphorus flame retardants are developmental neurotoxicants in a rat primary brainsphere in vitro model // Arch. Toxicol. 2021. V. 95. P. 207–228. https://doi.org/10.1007/s00204-020-02903-2Hogberg H.T., de Cássia da Silveira E Sá R., Kleensang A. et al. Organophosphorus flame retardants are developmental neurotoxicants in a rat primary brainsphere in vitro model // Arch. Toxicol. 2021. V. 95. P. 207–228. https://doi.org/10.1007/s00204-020-02903-2Carr R.L., Alugubelly N., de Leon K. et al. Inhibition of fatty acid amide hydrolase by chlorpyrifos in juvenile rats results in altered exploratory and social behavior as adolescents // Neurotoxicology. 2020. V. 77. P. 127–136. https://doi.org/10.1016/j.neuro.2020.01.002Carr R.L., Alugubelly N., de Leon K. et al. Inhibition of fatty acid amide hydrolase by chlorpyrifos in juvenile rats results in altered exploratory and social behavior as adolescents // Neurotoxicology. 2020. V. 77. P. 127–136. https://doi.org/10.1016/j.neuro.2020.01.002Супотницкий М.В. Химическое оружие в ирано-иракской войне 1980–1988 годов. 6. Накопленный опыт лечения поражений отравляющими веществами нервно-паралитического действия // Вестник войск РХБ защиты. 2022. Т. 6. № 1. С. 65–82. https://doi.org/10.35825/2587-5728-2022-6-1-65-82Supotnitskiy M.V. Chemical weapons in the IranIraq war (1980–1988). 6. Accumulated experience in the treatment of lesions with poisonous nerve agents // Journal of NBC Protection Corps. 2022. V. 6. № 1. P. 65– 82. https://doi.org/10.35825/2587-5728-2022-6-1-65-82 (in Russian).Quaak I., Brouns M.R., van de Bor M. The dynamics of autism spectrum disorders: how neurotoxic compounds and neurotransmitters interact // Int. J. Environ. Res. Public Health. 2013. V. 10. P. 3384–3408. https://doi.org/10.3390/ijerph10083384Quaak I., Brouns M.R., van de Bor M. The dynamics of autism spectrum disorders: how neurotoxic compounds and neurotransmitters interact // Int. J. Environ. Res. Public Health. 2013. V. 10. P. 3384–3408. https://doi.org/10.3390/ijerph10083384Han, SW., Shin, JS. Aromatic L-amino acid decarboxylases: mechanistic features and microbial applications // Appl. Microbiol. Biotechnol. 2022. V. 106. P. 4445–4458. https://doi.org/10.1007/s00253-022-12028-4Han, SW., Shin, JS. Aromatic L-amino acid decarboxylases: mechanistic features and microbial applications // Appl. Microbiol. Biotechnol. 2022. V. 106. P. 4445–4458. https://doi.org/10.1007/s00253-022-12028-4Bertoldi, M. Mammalian dopa decarboxylase: structure, catalytic activity and inhibition // Arch. Biochem. Biophys. 2014. V. 546. P. 1–7. https://doi.org/10.1016/j.abb.2013.12.020Bertoldi, M. Mammalian dopa decarboxylase: structure, catalytic activity and inhibition // Arch. Biochem. Biophys. 2014. V. 546. P. 1–7. https://doi.org/10.1016/j.abb.2013.12.020Shan L., Bao A.M., Swaab D.F. Changes in histidine decarboxylase, histamine N-methyltransferase and histamine receptors in neuropsychiatric disorders // In: Histamine and Histamine Receptors in Health and Disease. Handbook of Experiment. Pharmacology. V. 241 / Eds. Hattori Y., Seifert R. Cham, Switzerland: Springer, 2017. P. 259–276. https://doi.org/10.1007/164_2016_125Shan L., Bao A.M., Swaab D.F. Changes in histidine decarboxylase, histamine N-methyltransferase and histamine receptors in neuropsychiatric disorders // In: Histamine and Histamine Receptors in Health and Disease. Handbook of Experiment. Pharmacology. V. 241 / Eds. Hattori Y., Seifert R. Cham, Switzerland: Springer, 2017. P. 259–276. https://doi.org/10.1007/164_2016_125Dade M., Berzero G., Izquierdo C. et al. Neurological syndromes associated with Anti-GAD antibodies // Int. J. Mol. Sci. 2020. V. 21. P. e3701. https://doi.org/10.3390/ijms21103701Dade M., Berzero G., Izquierdo C. et al. Neurological syndromes associated with Anti-GAD antibodies // Int. J. Mol. Sci. 2020. V. 21. P. e3701. https://doi.org/10.3390/ijms21103701Martin D.L., Martin S.B., Wu S.J., Espina N. Cofactor interactions and the regulation of glutamate decarboxylase activity // Neurochem. Res. 1991. V. 16. № 3. P. 243–249. https://doi.org/10.1007/BF00966087Martin D.L., Martin S.B., Wu S.J., Espina N. Cofactor interactions and the regulation of glutamate decarboxylase activity // Neurochem. Res. 1991. V. 16. № 3. P. 243–249. https://doi.org/10.1007/BF00966087Giardina G., Montioli R., Gianni S. et al. Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases // Proc. Natl. Acad. Sci. U.S.A. 2011. V. 108. P. 20514– 20519. https://doi.org/10.1073/pnas.1111456108Giardina G., Montioli R., Gianni S. et al. Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases // Proc. Natl. Acad. Sci. U.S.A. 2011. V. 108. P. 20514– 20519. https://doi.org/10.1073/pnas.1111456108Aslanli A., Lyagin I., Stepanov N. et al. Bacterial cellulose containing combinations of antimicrobial peptides with various QQ enzymes as a prototype of an ‘enhanced antibacterial’ dressing: In silico and in vitro data // Pharmaceutics. 2020. V. 12. P. e1155. https://doi.org/10.3390/pharmaceutics12121155Aslanli A., Lyagin I., Stepanov N. et al. Bacterial cellulose containing combinations of antimicrobial peptides with various QQ enzymes as a prototype of an ‘enhanced antibacterial’ dressing: In silico and in vitro data // Pharmaceutics. 2020. V. 12. P. e1155. https://doi.org/10.3390/pharmaceutics12121155Aslanli A., Lyagin I., Efremenko E. Charges’ interaction in polyelectrolyte (nano)complexing of His6-OPH with peptides: Unpredictable results due to imperfect or useless concept? // Int. J. Biol. Macromol. 2019. V. 140. P. 368–376. https://doi.org/10.1016/j.ijbiomac.2019.08.137Aslanli A., Lyagin I., Efremenko E. Charges’ interaction in polyelectrolyte (nano)complexing of His6-OPH with peptides: Unpredictable results due to imperfect or useless concept? // Int. J. Biol. Macromol. 2019. V. 140. P. 368–376. https://doi.org/10.1016/j.ijbiomac.2019.08.137Lyagin I., Efremenko E. Theoretical evaluation of suspected enzymatic hydrolysis of Novichok agents // Catal. Commun. 2019. V. 120. P. 91–94. https://doi.org/10.1016/j.catcom.2018.11.019Lyagin I., Efremenko E. Theoretical evaluation of suspected enzymatic hydrolysis of Novichok agents // Catal. Commun. 2019. V. 120. P. 91–94. https://doi.org/10.1016/j.catcom.2018.11.019Harvey S.P., McMahon L.R., Berg F.J. Hydrolysis and enzymatic degradation of Novichok nerve agents // Heliyon. 2020. V. 6. P. e03153. https://doi.org/10.1016/j.heliyon.2019.e03153Harvey S.P., McMahon L.R., Berg F.J. Hydrolysis and enzymatic degradation of Novichok nerve agents // Heliyon. 2020. V. 6. P. e03153. https://doi.org/10.1016/j.heliyon.2019.e03153Nepovimova E., Kuca K. Chemical warfare agent NOVICHOK – mini-review of available data // Food Chem. Toxicol. 2018. V. 121. P. 343–350. https://doi.org/10.1016/j.fct.2018.09.015Nepovimova E., Kuca K. Chemical warfare agent NOVICHOK – mini-review of available data // Food Chem. Toxicol. 2018. V. 121. P. 343–350. https://doi.org/10.1016/j.fct.2018.09.015Hrvat N.M., Kovarik Z. Counteracting poisoning with chemical warfare nerve agents // Arh. Hig. Rada. Toksikol. 2020. V. 71. P. 266–284. https://doi.org/10.2478/aiht-2020-71-3459Hrvat N.M., Kovarik Z. Counteracting poisoning with chemical warfare nerve agents // Arh. Hig. Rada. Toksikol. 2020. V. 71. P. 266–284. https://doi.org/10.2478/aiht-2020-71-3459Aslanli A., Lyagin I., Efremenko E. Decarboxylases as hypothetical targets for actions of organophosphates: Molecular modeling for prediction of hidden and unexpected health threats // Food Chem. Toxicol. 2022. V. 161. P. 112856. https://doi.org/10.1016/j.fct.2022.112856Aslanli A., Lyagin I., Efremenko E. Decarboxylases as hypothetical targets for actions of organophosphates: Molecular modeling for prediction of hidden and unexpected health threats // Food Chem. Toxicol. 2022. V. 161. P. 112856. https://doi.org/10.1016/j.fct.2022.112856Lyagin I., Efremenko E. Enzymes, reacting with organophosphorus compounds as detoxifiers: Diversity and functions // Int. J. Mol. Sci. 2021. V. 22. P. e1761. https://doi.org/10.3390/ijms22041761Lyagin I., Efremenko E. Enzymes, reacting with organophosphorus compounds as detoxifiers: Diversity and functions // Int. J. Mol. Sci. 2021. V. 22. P. e1761. https://doi.org/10.3390/ijms22041761Efremenko E.N., Lyagin I.V., Klyachko N.L. et al. A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins // J. Control Release. 2017. V. 247. P. 175–181. https://doi.org/10.1016/j.jconrel.2016.12.037Efremenko E.N., Lyagin I.V., Klyachko N.L. et al. A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins // J. Control Release. 2017. V. 247. P. 175–181. https://doi.org/10.1016/j.jconrel.2016.12.037Nandi N.K., Vyas A., Akhtar Md. J., Kumar B. The growing concern of chlorpyrifos exposures on human and environmental health //Pesticide Biochem. Physiol. 2022. V. 185. P. 105138. https://doi.org/10.1016/j.pestbp.2022.105138Nandi N.K., Vyas A., Akhtar Md. J., Kumar B. The growing concern of chlorpyrifos exposures on human and environmental health //Pesticide Biochem. Physiol. 2022. V. 185. P. 105138. https://doi.org/10.1016/j.pestbp.2022.105138Tarazona J., Court M.D., Tiramani M. et al. Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC // Arch. Toxicol. 2017. V. 91. P. 2723–2743. https://doi.org/10.1007/s00204-017-1962-5Tarazona J., Court M.D., Tiramani M. et al. Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC // Arch. Toxicol. 2017. V. 91. P. 2723–2743. https://doi.org/10.1007/s00204-017-1962-5Costas-Ferreira C., Durán R., Faro L. Toxic effects of glyphosate on the nervous system: a systematic review // Intern. J. Molec. Sci. 2022. V. 23. P. 4605. https://doi.org/10.3390/ijms23094605Costas-Ferreira C., Durán R., Faro L. Toxic effects of glyphosate on the nervous system: a systematic review // Intern. J. Molec. Sci. 2022. V. 23. P. 4605. https://doi.org/10.3390/ijms23094605Norrrahim M.N.F., Razak M.A.I.A., Shah N.A.A. et al. Recent developments on oximes to improve the blood brain barrier penetration for the treatment of organophosphorus poisoning: a review // RSC Adv. 2020. V. 10. P. 4465–4489. https://doi.org/10.1039/c9ra08599hNorrrahim M.N.F., Razak M.A.I.A., Shah N.A.A. et al. Recent developments on oximes to improve the blood brain barrier penetration for the treatment of organophosphorus poisoning: a review // RSC Adv. 2020. V. 10. P. 4465–4489. https://doi.org/10.1039/c9ra08599hKaur S., Singh S., Jaiswal G. et al. Pharmacology of dopamine and its receptors // In: Frontiers in Pharmacology of Neurotransmitters / Eds. Kumar P., Deb P.K. Singapore: Springer, 2020. Chapter 5, P. 143– 182. https://doi.org/10.1007/978-981-15-3556-7_5Kaur S., Singh S., Jaiswal G. et al. Pharmacology of dopamine and its receptors // In: Frontiers in Pharmacology of Neurotransmitters / Eds. Kumar P., Deb P.K. Singapore: Springer, 2020. Chapter 5, P. 143– 182. https://doi.org/10.1007/978-981-15-3556-7_5Speranza L., di Porzio U., Viggiano D. et al. Dopamine: the neuromodulator of long-term synaptic plasticity, reward and movement control // Cells. 2021. V. 10. P. e735. https://doi.org/10.3390/cells10040735Speranza L., di Porzio U., Viggiano D. et al. Dopamine: the neuromodulator of long-term synaptic plasticity, reward and movement control // Cells. 2021. V. 10. P. e735. https://doi.org/10.3390/cells10040735Moya-García A.A., Pino-Ángeles A., GilRedondo R. et al. Structural features of mammalian histidine decarboxylase reveal the basis for specific inhibition // Br. J. Pharmacol. 2009. V. 157. P. 4–13. https://doi.org/10.1111/j.1476-5381.2009.00219.xMoya-García A.A., Pino-Ángeles A., GilRedondo R. et al. Structural features of mammalian histidine decarboxylase reveal the basis for specific inhibition // Br. J. Pharmacol. 2009. V. 157. P. 4–13. https://doi.org/10.1111/j.1476-5381.2009.00219.xHan, SW., Shin, JS. Aromatic L-amino acid decarboxylases: mechanistic features and microbial applications // Appl. Microbiol. Biotechnol. 2022. V. 106. P. 4445–4458. https://doi.org/10.1007/s00253-022-12028-4Han, SW., Shin, JS. Aromatic L-amino acid decarboxylases: mechanistic features and microbial applications // Appl. Microbiol. Biotechnol. 2022. V. 106. P. 4445–4458. https://doi.org/10.1007/s00253-022-12028-4Jiang M, Xu G, Ni J. et al. Improving soluble expression of tyrosine decarboxylase from Lactobacillus brevis for tyramine synthesis with high total turnover number // Appl. Biochem. Biotechnol. 2019. V. 188. P. 436–449. https://doi.org/10.1007/s12010-018-2925-xJiang M, Xu G, Ni J. et al. Improving soluble expression of tyrosine decarboxylase from Lactobacillus brevis for tyramine synthesis with high total turnover number // Appl. Biochem. Biotechnol. 2019. V. 188. P. 436–449. https://doi.org/10.1007/s12010-018-2925-xChoi Y., Han S.-W., Kim J.-S. et al. Biochemical characterization and synthetic application of aromatic L-amino acid decarboxylase from Bacillus atrophaeus // Appl. Microbiol. Biotechnol. 2021. V. 105. P. 2775–2785. https://doi.org/10.1007/s00253-021-11122-3Choi Y., Han S.-W., Kim J.-S. et al. Biochemical characterization and synthetic application of aromatic L-amino acid decarboxylase from Bacillus atrophaeus // Appl. Microbiol. Biotechnol. 2021. V. 105. P. 2775–2785. https://doi.org/10.1007/s00253-021-11122-3Nakagawa A., Nakamura S., Matsumura E. et al. Selection of the optimal tyrosine hydroxylation enzyme for (S)-reticuline production in Escherichia coli // Appl. Microbiol. Biotechnol. 2021. V. 105. P. 5433– 5447. https://doi.org/10.1007/s00253-021-11401-zNakagawa A., Nakamura S., Matsumura E. et al. Selection of the optimal tyrosine hydroxylation enzyme for (S)-reticuline production in Escherichia coli // Appl. Microbiol. Biotechnol. 2021. V. 105. P. 5433– 5447. https://doi.org/10.1007/s00253-021-11401-z

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