Biosynthetic investigations of the V-type ATPase inhibitors bafilomycin A1, B1 and concanamycin A.
The plecomacrolides bafilomycin A1 and B1 (1, 2) and concanamycin A (3), produced by different Streptomyces species, show a unique macrolactone structure with characteristic side chains and exhibit striking biological activities including distinct V-type ATPase inhibition. The biosynthesis of 1 and 2 has been established by feeding experiments with 13C-labelled precursors. Both, bafilomycin (1, 2) and concanamycin (3) feature an "unusual C2 chain extension unit" of as yet unknown origin which was addressed by feeding labelled 2-hydroxy- and 2-methoxymalonyl-derivatives.
Schuhmann
Tim
T
Institut für Organische und Biomolekulare Chemie, Universität Göttingen, Germany.
Grond
Stephanie
S
D004791:Enzyme Inhibitors / Q000378:metabolism*; D018942:Macrolides / Q000378:metabolism*; D013302:Streptomyces / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D018942:Macrolides; C036978:concanamycin A; C040929:bafilomycin A1; C052501:bafilomycin B1; D025262:Vacuolar Proton-Translocating ATPases