Title: Biocatalytic transformation of the progesterone by the Aspergillus nidulans VKPM F-1069 and by the genetically modified strains obtained on its basis

Biography:

Olga Savinova is a junior researcher at the Laboratory of Molecular Aspects of Biotransformations, A. N. Bach Institute of Biochemistry, Research Center of Biotechnology, RAS. She has participated in various international conferences and has publications in the leading scientific journals. Her scientific interests: involves biocatalytic transformation of steroids by filamentous fungi, heterologous expression of enzymes in ascomycetes, the study of the proteome and secretome of fungi.

Abstract

The targeted introduction of various functional groups in the steroid molecule determines the diversity of physiological activities of the compound. Hydroxylation of the progesterone (PG, I) has great scientific and practical interest. However, 11-hydroxylation of PG in a single stage with a high degree of regio- and stereo- selectivity is only possible biotechnologically using microorganisms (mainly filamentous fungi) enzyme systems. The present study investigated the ability of the A. nidulans VKPM F-1069 (syn. FGSC A4) and genetically modified strains A.nidulans 031(argB^-, pyrG^-) (syn. AN031), A.nidulans lacâ„–4 (argB^-), and A.nidulans 031/pN8 (pyrG^-) to transform PG. It was established that all used strains are capable to transform of PG with the formation of 3 main products: 11α-hydroxy-PG (II), 11α-acetoxy-PG(III) and 6β,11α-dihydroxy-PG(IV), but in different ratio. However, the accumulation of 11α-hydroxy-PG does not occur, since it is further modified into compounds III and IV. 11α-Acetoxy-PG can be converted into compound II by the known methods of hydrolysis. The maximum total relative selectivity of the compounds II and III formation (68.4% mol) was observed during the transformation of PG by the A.nidulans lacâ„–4 strain. The yield of the target products can be increased by optimizing the cultivation conditions of the strain and transformation conditions. The ability of Aspergillus fungi to acetylate 11α-hydroxy-PG has been established by us for the first time. The compounds II и III are of interest not only as precursors in the synthesis of highly active steroid drugs, but also as independent drugs with gestagen and antiandrogenic activity.