Production of a new thiopeptide antibiotic, TP-1161, by a marine Nocardiopsis species.
Twenty-seven marine sediment- and sponge-derived actinomycetes with a preference for or dependence on seawater for growth were classified at the genus level using molecular taxonomy. Their potential to produce bioactive secondary metabolites was analyzed by PCR screening for genes involved in polyketide and nonribosomal peptide antibiotic synthesis. Using microwell cultures, conditions for the production of antibacterial and antifungal compounds were identified for 15 of the 27 isolates subjected to this screening. Nine of the 15 active extracts were also active against multiresistant gram-positive bacterial and/or fungal indicator organisms, including vancomycin-resistant Enterococcus faecium and multidrug-resistant Candida albicans. Activity-guided fractionation of fermentation extracts of isolate TFS65-07, showing strong antibacterial activity and classified as a Nocardiopsis species, allowed the identification and purification of the active compound. Structure elucidation revealed this compound to be a new thiopeptide antibiotic with a rare aminoacetone moiety. The in vitro antibacterial activity of this thiopeptide, designated TP-1161, against a panel of bacterial strains was determined.
Engelhardt
Kerstin
K
Norwegian University of Science and Technology, Department of Biotechnology, Sem Saelandsvei 6/8, 7491 Trondheim, Norway.
Degnes
Kristin F
KF
Kemmler
Michael
M
Bredholt
Harald
H
Fjaervik
Espen
E
Klinkenberg
Geir
G
Sletta
Håvard
H
Ellingsen
Trond E
TE
Zotchev
Sergey B
SB
D000192:Actinomycetales / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D000935:Antifungal Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D005800:Genes, Fungal; D019015:Geologic Sediments / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D011161:Porifera / Q000382:microbiology*; D017422:Sequence Analysis, DNA
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D010455:Peptides