Food Processing: Techniques and Technology Food Processing: Techniques and Technology Техника и технология пищевых производств 2074-9414 2313-1748 57621 10.21603/2074-9414-2023-1-2419 ОБЗОРНАЯ СТАТЬЯ REVIEW ARTICLE ОБЗОРНАЯ СТАТЬЯ Biotechnology of Lactulose Production: Progress, Challenges, and Prospects Биотехнология лактулозы: современные достижения, проблемы и перспективы https://orcid.org/0000-0001-9803-8709 Рябцева Светлана Андреевна Ryabtseva Svetlana A. ryabtseva07@mail.ru https://orcid.org/0000-0002-5188-4657 Храмцов Андрей Георгиевич Khramtsov Andrey G.

доктор технических наук;

doctor of technical sciences;

 https://orcid.org/0000-0002-0119-9061 Шпак Мария Александровна Shpack Maria A. https://orcid.org/0000-0001-8460-2954 Лодыгин Алексей Дмитриевич Lodygin Alexei D. allodygin@yandex.ru https://orcid.org/0000-0001-9257-9571 Анисимов Георгий Сергеевич Anisimov Georgy S. https://orcid.org/0000-0002-8200-3007 Сазанова Серафима Николаевна Sazanova Serafima N. Табакова Юлия Александровна Tabakova Yulia A. Северо-Кавказский федеральный университет Ставрополь Россия North-Caucasus Federal University Stavropol Russian Federation Северо-Кавказский федеральный университет Ставрополь Россия North-Caucasus Federal University Stavropol Russian Federation Северо-Кавказский федеральный университет Ставрополь Россия North-Caucasus Federal University Stavropol Russian Federation Северо-Кавказский федеральный университет Ставрополь Россия North-Caucasus Federal University Stavropol Russian Federation Северо-Кавказский федеральный университет Ставрополь Россия North Caucasus Federal University Stavropol Russian Federation АО Молочный комбинат «Ставропольский» Ставрополь Россия JSC Stavropolskiy Dairy Plant Stavropol Russian Federation Северо-Кавказский федеральный университет Ставрополь Россия North-Caucasus Federal University Stavropol Russian Federation Северо-Кавказский федеральный университет Ставрополь Россия North-Caucasus Federal University Stavropol Russian Federation 27 03 2023 27 03 2023 53 1 97 122 14 09 2022 06 12 2022 https://fptt.ru/en/issues/21374/21406/

Лактулоза является пребиотиком, который широко применяется в медицине и пищевой промышленности. Производство лактулозы основано на изомеризации лактозы в щелочных средах при высоких температурах. Альтернативой являются ферментативные способы, которые считаются более экологически чистыми и позволяют проводить процессы в более мягких условиях. Объектом исследования стали научные публикации по вопросам синтеза и очистки лактулозы с использованием ферментов. Для поиска информации были использованы базы данных Scopus, Web of Science, PubMed и Elibrary за период с 1978 по 2022 гг. Рассмотрели два основных пути ферментативного превращения лактозы в лактулозу: изомеризация (прямой) и трансгалактозилирование (с промежуточным гидролизом). Для первого применяют целлюлозо-2-эпимеразы, которые пока не имеют статуса безопасности и их не производят в промышленных масштабах, а побочным продуктом их реакции является эпилактоза. Для трансгалактозилирования применяют β-галактозидазы, которые имеют международный статус безопасности (GRAS) и доступны на рынке, с хорошо изученным механизмом действия. Систематизировали данные об условиях получения максимальных выходов лактулозы при использовании разных ферментов. Основными продуцентами β-галактозидаз для получения лактулозы являются дрожжи Kluyveromyces lactis и плесени Aspergillus оryzae. Выход лактулозы достигает 30 % в оптимальных условиях. Основной проблемой является необходимость внесения фруктозы. Прямой зависимости между максимальными выходами лактулозы и молярными соотношениями фруктоза:лактоза не выявлено. Применение целлобиозо-эпимераз позволяет достигать высоких выходов лактулозы (70–80 %), но для получения этих ферментов используют методы генной инженерии и мутагенеза, что ставит под сомнение их безопасность. К наиболее перспективным тенденциям развития биотехнологии лактулозы можно отнести использование вторичного молочного сырья и иммобилизованных ферментов, применение разных моделей реакторов, в т. ч. мембранных, и разработку комплексных взаимосвязанных процессов получения ферментов, конверсии лактозы в лактулозу и очистки готовых продуктов.

Lactulose is a prebiotic that has found a wide application in medicine and food industry. Commercial lactulose is usually synthesized by isomerization in alkaline media at high temperatures. Enzymatic methods offer a more sustainable alternative and require more moderate processing conditions. This review covers 44 years of scientific publications (1978–2022) on the enzymatic synthesis and purification of lactulose. The materials were retrieved from Scopus, Web of Science, PubMed, and Elibrary databases. The enzymatic approach to lactose-to-lactulose conversion has two methods: isomerization (direct) and transgalactosylation (via hydrolysis). Isomerization exploits cellulose-2-epimerases, but their safety status is still rather vague. As a result, cellulose-2-epimerases are not commercial. Epilactose is a by-product of isomerization. Transgalactosylation involves β-galactosidases with an official international safety status (GRAS). It is available on the market, and its action mechanism is well understood. This article systematizes various data on the conditions for obtaining the maximal yields of lactulose by different enzymes. The Kluyveromyces lactis yeast and the Aspergillus oryzae mold are the main sources of β-galactosidases in lactulose production. The yield can reach 30% if the processing conditions are optimal. Fructose remains the main problem in the production process. No scientific publications revealed a direct relationship between the maximal yields of lactulose and the molar fructose-tolactose ratios. Cellobiose epimerases make it possible to achieve high yields of lactulose (70–80%). However, these enzymes are associated with genetic engineering and mutagenesis, which challenges their safety status. The most promising trends in lactulose biotechnology include secondary dairy raw materials, immobilized enzymes, membrane reactors, complex production processes, lactose-to-lactulose conversion, and purification of final product.

 Лактулоза лактоза биоконверсия ферменты выход β-галактозидаза Kluyveromyces Aspergillus целлобиозо-2-эпимераза тенденции Lactulose lactose bioconversion enzymes yield β-galactosidase Kluyveromyces Aspergillus cellobiose-2- epimerase trends Работа выполнена при финансовой поддержке Министерства науки и высшего образования Российской Федерации (Минобрнауки России) в рамках реализации комплексного проекта по созданию высокотехнологичного производства по теме «Создание первого в России высокотехнологичного производства пребиотика лактулозы и функциональных молочных ингредиентов для импортозамещения в медицине, ветеринарии, детском питании, производстве лечебно-профилактических продуктов для людей и животных» (Соглашение о предоставлении из федерального бюджета субсидии на развитие кооперации государственного научного учреждения и организации реального сектора экономики в целях реализации комплексного проекта по созданию высокотехнологичного производства № 075-11-2022-021 от 07.04.2022 г.) и в рамках Постановления Правительства РФ от 9 апреля 2010 г. № 218 на базе Северо-Кавказского федерального университета (СКФУ) . The research was supported by the Ministry of Science and Higher Education of the Russian Federation (Minobrnauka) as part of a comprehensive high-tech production project on the topic “The first Russian high-tech production of lactulose prebiotic and functional dairy ingredients for import substitution in medicine, veterinary, baby food, and medical preventive products for people and animals”, Decree No. 218 of the Government of the Russian Federation of April 9, 2010. The subsidies were allocated from the Federal Budget for the development of cooperation between state scientific institutions and the real sector of the economy as part of a comprehensive high-tech production project No. 075-11-2022-021 of 04/07/2022. The research was conducted on the premises of the North-Caucasus Federal University (NCFU).

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