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Biosynthesis of Colabomycin E, a New Manumycin-Family Metabolite, Involves an Unusual Chain-Length Factor
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SYSNO ASEP 0434468 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Biosynthesis of Colabomycin E, a New Manumycin-Family Metabolite, Involves an Unusual Chain-Length Factor Author(s) Petříčková, Kateřina (MBU-M) RID
Pospíšil, Stanislav (MBU-M) RID
Kuzma, Marek (MBU-M) ORCID, RID
Tylová, Tereza (MBU-M)
Jágr, Michal (MBU-M)
Tomek, P. (CZ)
Chroňáková, Alica (BC-A) RID, ORCID
Brabcová, E. (CZ)
Anděra, Ladislav (UMG-J) RID
Krištůfek, Václav (BC-A) RID
Petříček, Miroslav (MBU-M) RIDSource Title Chembiochem. - : Wiley - ISSN 1439-4227
Roč. 15, č. 9 (2014), s. 1334-1345Number of pages 12 s. Language eng - English Country DE - Germany Keywords biosynthesis ; chain-length factors ; manumycins Subject RIV CE - Biochemistry R&D Projects NT13012 GA MZd - Ministry of Health (MZ) Institutional support MBU-M - RVO:61388971 ; BC-A - RVO:60077344 ; UMG-J - RVO:68378050 UT WOS 000337638400016 DOI 10.1002/cbic.201400068 Annotation Colabomycin E is a new member of the manumycin-type metabolites produced by the strain Streptomyces aureus SOK1/5-04 and identified by genetic screening from a library of streptomycete strains. The structures of colabomycin E and accompanying congeners were resolved. The entire biosynthetic gene cluster was cloned and expressed in Streptomyces lividans. Bioinformatic analysis and mutagenic studies identified components of the biosynthetic pathway that are involved in the formation of both polyketide chains. Recombinant polyketide synthases (PKSs) assembled from the components of colabomycin E and asukamycin biosynthetic routes catalyzing the biosynthesis of "lower" carbon chains were constructed and expressed in S. aureus SOK1/5-04 Delta colC11-14 deletion mutant. Analysis of the metabolites produced by recombinant strains provided evidence that in both biosynthetic pathways the length of the lower carbon chain is controlled by an unusual chain-length factor supporting biosynthesis either of a triketide in asukamycin or of a tetraketide in colabomycin E. Biological activity assays indicated that colabomycin E significantly inhibited IL-1 beta release from THP-1 cells and might thus potentially act as an anti-inflammatory agent Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2015
Number of the records: 1