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History of Science and Engineering

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LABORATORY OF MICROBIAL TRANSFORMATION OF ORGANIC COMPOUNDS, IBPM RAS: CREATION, ESTABLISHMENT AND PROGRESS
M.V. Donova, V.V. Fokina

The Laboratory of Microbial Transformation of Organic Compounds (MTOC) had been created in 1989 and is having the roots from the research group at the Department of microbial transformation of organic compounds (headed by Academician George Skryabin). Professor, DSci Kira Koshcheyenko had been in charge of the Laboratory until 1997. Major research fields of the laboratory include studies of microbial diversity of steroid transforming organisms, biocatalytic properties of microorganisms towards different steroid compounds, sterol catabolism by actinobacteria, biotransformation of natural and synthetic steroids, creation of biocatalytic systems for the directed synthesis of physiologically active steroids on the base of genetic and metabolic engineering of microbial strains, bioprocess development for obtaining value-added steroid and isoprenoid compounds and full-cycle technologies for production of the active pharmaceutical ingredients and intermediates. The collection of steroid-transforming strains that performed structural modifications of steroids has been created and is continuously fulfilling. This collection includes the strains capable of performing cascades of the oxidative degradation of sterol sidechain, steroid core oxyfunctionalization, introduction, isomerization and reduction of the C-C double bonds, steroid alcohols oxidation, carbonyl groups reduction, steroid esters hydrolysis etc. Based on the results of the “-omic”s (genomics, transcriptomics, metabolomics, etc.) investigations, priority data had been obtained on the peculiarities of organization and functionality of the sterol catabolism genes in actinobacteria, key gene patterns had been revealed which are essential for re-direction of the metabolic pathways towards target steroid formation. Effective recombinant strains of mycobacteria representing cell biocatalysts of new generation have been created that perform cascade reactions of sidechain oxidation and structural modification of steroid core to produce important pharmaceutical steroids and other isoprenoids. Methodology for heterologous expression of the eukaryotic steroidogenesis system in bacterial hosts has been developed and the recombinant strains have been obtained capable of producing value-added steroid hormones in a single stage from natural sterols. Totally, over 20 biotechnologies/biotech methods for production of value-added steroids from renewable plant sterols, or sterol containing industrial wastes had been developed. Few technologies had been scaled up to the semi-industrial level. Manufacturing application will affect productions of pharmaceutical steroids including corticosteroids, mineralocorticoids, neurosteroids, bile acids etc.
Keywords: IBPM RAS, microbial transformation, bioconversion, steroids, genetic engineering, biotechnology, microbiology, PSCBR RAS.


DOI: 10.25791/intstg.06.2020.1188

Pp. 24-35.

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