Biosynthetic Investigations of the V-Type ATPase Inhibitors Bafilomycin A₁, B₁ and Concanamycin A

Abstract

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-hydroxyand 2-methoxymalonyl-derivatives.