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Registration Number

0225U000194, (0124U002533) , R & D reports

Title

Biotechnological and pharmacological potential of new antibiotic Je478 with the antimycobacterial activity

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Шлях біосинтезу Je478 та характеристика мінімального БКГ Je478 та конструювання штамів з підвищеною продукцією Je478 методами геномної та метаболічної інженерії.

Head

Fedorenko Viktor O., д.б.н.

Registration Date

07-01-2025

Organization

Ivan Franko National University of Lviv

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Elucidate the genetic control of Je478 biosynthesis and using this knowledge to construct the platform for Je478 production based on biotechnologically improved strains of actinomycetes

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 According to the results of phylogenetic analysis, the Je 1-332 strain, the producer of the Je478 antibiotic, is classified as a representative of the Streptomyces genus. A morphological description of Streptomyces sp. Je1-332 was carried out, its cultural and physiological and biochemical characteristics were determined. Optimal conditions for its cultivation for the production of the Je478 antibiotic and genetic manipulations were selected. A gene cloning system was developed in the Streptomyces sp. Je1-332 strain. The Streptomyces sp. Je1-332 genome was sequenced and annotated. Using functional annotation of the Je1-332 genome, 20 groups of its genes were identified, which are involved in its various metabolic pathways. 21 clusters of secondary metabolism genes were identified in the Je1-332 genome. A cosmid library of Streptomyces sp. Je1-332 with a genome coverage of 99.5%. Heterologous expression of the Je478 antibiotic biosynthesis gene cluster was carried out in the S. albus Del14 model strain by transferring the P4-E01-AmInt cosmid into it. The search for genes involved in Je478 biosynthesis was carried out using mutagenesis caused by the Tn5 transposon. Cloning and sequencing of the Tn5 insertion loci made it possible to identify a chromosome region containing the Je478 biosynthesis gene cluster. Bioinformatic analysis of the genes of this region revealed 12 genes that presumably control the biosynthesis of Je478. The results obtained became the basis for experimental studies of the genes and biosynthesis pathway of the Je478 antibiotic, and the development of approaches to obtaining improved Je478-producing strains. An application for the invention “Streptomyces sp. Actinomycete strain IMВ Ac-5052 – producer of guanidine-containing triterpene antibiotic Je478” has been filed, application for the invention No. a202302796; filed on 08.06.2023; applicant Ivan Franko National University of Lviv; authors Gromyko O.M., Tistechok S.I., Fedorenko V.O

Product Description

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Bilyk Bohdan R.
Hromyko Oleksandr M.
Vasyl Y. Syrvatka
Tistechok Stepan I.

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2025-01-07