THE STUDY OF POSSIBILITY OF BIOLOGICALLY ACTIVE AGENTS SORPTION FROM CULTURE LIQUID ON THE EXAMPLE OF COPROPORPHYRIN III

Authors

  • Stanislav N. Mishutkin ELEST Co. Ltd., St. Petersburg
  • Philipp V. Bondarenko Saint-Petersburg State Institute of Technology, St. Petersburg
  • Mark A. Malkov ELEST Co. Ltd., St. Petersburg
  • Nikita V. Malkov ELEST Co. Ltd., St. Petersburg
  • Dmitry O. Vinokhodov Saint-Petersburg State Institute of Technology, St. Petersburg
  • Anatoly I. Ginak Saint-Petersburg State Institute of Technology, St. Petersburg

Keywords:

coproporphyrin III, pulsed fluidized mode, extraction, purification, a bacterial cell, sorption, desorption, culture liquid, technology, biologically active agent.

Abstract

At release of biologically active agents received by means of microbiological synthesis one of
the first stages is filtration of culture liquid with native solution receiving. This stage is especially
labor-consuming if a producer of target substance is the bacterial cell with the size about 1 micron
as insoluble residues of nutrient medium and metabolites of a producer and also cells clog the filtering
surface, thereby increasing hydrodynamic drag force so that filtration practically stops. Various
expensive methods, for example, regular updating of a filter blanket by mechanical removal
of the top part of a filter blanket together with solid fraction of culture liquid are used to overcome
this problem. Such method is applied on drum filters. Drum filters are of large size, take a lot of
place at the plant and are expensive producing and operating. The present article considers the
possibility of filtration stage replacement with more technological process of sorption of a main
product immediately from cultural liquid, using the example of coproporphyrin III a producer of
which is Arthrobacter globiformis bacterium with cell sizes of about 1 micron. The technology of
coproporphyrin III extracting and its purification with coproporphyrin III sorption immediately
from culture liquid without biomass separation in pulsed fluidized mode with the subsequent desorption
was developed. Further stages of extracting and purification include settling of target substance
by means of the solution рН value change, porphyrine extraction from the precipitation,
chromatographic purification on a molecular sorbent, the transfering of coproporphyrin III to potassium
salt and drying. The technology was tested in vitro and the coproporphyrin III with high
degree of cleaning was obtained.

Author Biographies

Stanislav N. Mishutkin, ELEST Co. Ltd., St. Petersburg

Process Engineer

Philipp V. Bondarenko, Saint-Petersburg State Institute of Technology, St. Petersburg

Biotechnologist-microbiologist, ELEST Co. Ltd., St. Petersburg; a Post-Graduate Student of department of molecular biotechnology

Mark A. Malkov, ELEST Co. Ltd., St. Petersburg

candidate of Biology, Research Director

Nikita V. Malkov, ELEST Co. Ltd., St. Petersburg

deputy Research Director

Dmitry O. Vinokhodov, Saint-Petersburg State Institute of Technology, St. Petersburg

Dr. Sci. Biol., Head of the Departments of Molecular biotechnology, Associate professor

Anatoly I. Ginak, Saint-Petersburg State Institute of Technology, St. Petersburg

Doctor of Chemistry, professor of Department of Molecular biotechnology

References

Малков М.А., Петрищев Н.Н., Мишуткин С.Н. Разработка способа фотодинамической терапии для лечения неопластических новообразований с использованием фотосенсибилизатора на основе препарата копропорфирин // Фундаментальные исследования. – 2008. – № 1. – С. 142–146.

Antonio C.Tedesco, Fernando L.Primo, Priscila da Costa Carvalho de Jesus. Antimicrobial Photodynamic Therapy (APDT) Action Based on Nanostructured Photosensitizers // Multifunctional Systems for Combined Delivery, Biosensing and Diagnostics. – 2017. – Р. 9–29.

Juan Zhang, Chengshi Jiang, João Paulo Figueiró Longo et al. An updated overview on the development of new photosensitizers for anticancer photodynamic therapy // Acta Pharmaceutica Sinica B. – 2018. – Vol. 8, Iss. 2. – P. 137–146.

Быховский В.Я., Зайцева Н.И., Полулях О.В. Микробиологический синтез порфиринов / ВНИИСЭНТИ. – М., 1985. – С. 1–7.

Process for separating porphyrins / Maruhashi kenji [JP]; Kojima ichiro [JP]; Oguchi yutaka [JP]; Endoh noboru [JP]; Satoh tetsuo [JP] // US patent no. 4436663, 1984.

Полатовская О.Г., Барабанщикова Г.В., Малков М.А. и др. Штамм бактерий Arthrobacter Globiformis – продуцент копропорфирина III и способ получения копропорфирина III. Патент Российской Федерации № 2078138, 1993.

Быховский В.Я., Зайцева З.И., Радина В.П. и др. Метод выделения копропорфирина III. Авторское свидетельство № 1482946, 1978.

Falk G.E. Porphyrins and metalloporphyrins. – Amsterdam, New York, Oxford, Elsevier sci. publ. comp., 1964.

Мишуткин С.Н., Момот Н.Н. Разработка метода анализа содержания копропорфирина III в культуральной жидкости // Журнал прикладной химии. – 2005. – Т. 78, Вып. 11. – С. 1864–1867.

Мишуткин С.Н., Малков М.А. Изучение кинетики сорбции копропорфирина III на различных катионитах // Биотехнология. – 2009. – № 1. – С. 83–89.

Самсонов Г.В., Тростянская Е.Б., Елькин Г.Э. Ионный обмен. Сорбция органических веществ. – Л.: Наука, 1969. – С. 240, 245, 259, 264.

Кокотов Ю.А., Золотарев П.П., Елькин Г.Э. Теоретические основы ионного обмена: Сложные ионообменные системы. – Л.: Химия, 1986. – 280 с.

Goldstein S. Proc. Roy. Soc., A219. 171. 1953.

Patterson S. Proc. Physic. Soc. (London), 59, 50, 1947.

Малков М.А., Мишуткин С.Н., Момот Н.Н. Изучение сорбционных свойств кремнеземных сорбентов. Предмет изучения – копропорфирин III // Современные наукоемкие технологии. – 2005. – № 8. – С. 35–36.

Published

2019-09-30

Issue

Section

Environmental problems of biochemistry and technology