Isolation, structural elucidation, and biosynthesis of 15-norlankamycin derivatives produced by a type-II thioesterase disruptant of Streptomyces rochei

Autor:	Kenji Arakawa, Haruyasu Kinashi, Zhisheng Cao, Natsumi Suzuki
Rok vydání:	2011
Předmět:	chemistry.chemical_classification biology Stereochemistry Streptomycetaceae Organic Chemistry biology.organism_classification Biochemistry Streptomyces chemistry.chemical_compound Isobutyryl-CoA Enzyme chemistry Thioesterase Biosynthesis Drug Discovery Actinomycetales Gene
Zdroj:	Tetrahedron. 67:5199-5205
ISSN:	0040-4020
Popis:	Lankamycin, a 14-membered macrolide antibiotic, contains a 3-hydroxy-2-butyl side chain at C-13. To analyze the function of lkmE, which encodes type-II thioesterase in the lankamycin cluster, we carried out a gene disruption experiment. Disruption of lkmE resulted in a 70% decrease of lankamycin production concomitant with an accumulation of novel lankamycin derivatives (LM-NS01A and LM-NS01B), in which the C-13 side chain is replaced by a 1-carboxyethyl group. The biosynthetic origin of 1-carboxyethyl group was confirmed by incorporation of deuterium in [3-2H]3-methyl-2-oxobutyrate into the C-14 position. These results indicate that the biosynthesis of LM-NS01A and LM-NS01B starts from isobutyryl CoA in place of (S)-2-methylbutyryl CoA and LkmE removes the aberrantly loaded starter unit and restores lankamycin production.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::48cb46018017b76de1fc4f4da87b53db https://doi.org/10.1016/j.tet.2011.05.047 Zobrazit plný text záznamu Full Text from ScienceDirect