The biosynthesis of caerulomycins in Streptomyces caeruleus. Isolation of a new caerulomycin and incorporation of picolinic acid and glycerol into caerulomycin A

Abstract

Oxidation with permanganate of caerulomycin A labeled biosynthetically from [U-14C]lysine in cultures of Streptomyces caeruleus yielded picolinic acid with the same specific activity as the antibiotic. [3H]Picolinic acid was incorporated into caerulomycin A with high efficiency and the label was also found exclusively in picolinic acid after oxidation, implicating free picolinic acid as an intermediate in the pathway from lysine. The substituted pyridyl ring of caerulomycin was labeled by [2-13C, 1,3-14C]glycerol. 13C nuclear magnetic resonance analysis located the 13C predominantly at C-6, suggesting that C-5, C-6, and C-7 were derived from glycerol as an intact three-carbon precursor. Since no incorporation of [1-13C]glyceric acid was detected and [3-13C, 3-14C]methylglyoxal labeled the antibiotic only marginally, these compounds are probably not biosynthetic intermediates en route from glycerol. A new caerulomycin possessing an aldehyde in place of the aldoxime substituent at C-6 was isolated from culture broths and is postulated to be a late intermediate in the formation of caerulomycin A.