Curromycin B

We cloned six different DNA fragments from a curromycin producing strain, Streptomyces hygroscopicus 358AV2, which confer curromycin-resistance on a curromycin non-producing and sensitive strain, S. hygroscopicus Rgll, a protoplast regenerant of the strain 358AV2. We studied the plasmid pSHR2 carrying one of the DNA fragments. By Southern blot analysis, the cloned DNA sequence in pSHR2 was found to be deleted in the Rgll genome. From the Rgll strain, a curromycin producing revertant A-4 was obtained, indicating that the structural genes for the curromycin biosynthesis and resistance are retained in the Rgll genome. Based on the existence of A-4 and the deletion of the DNA region corresponding to the cloned DNA sequence in the Rgll genome, we conclude that the cloned DNA sequence carries a regulatory gene governing curromycin-resistance but not the resistance gene itself. The smallest DNA region in pSHR2 conferring curromycin-resistance was sequenced, and it was found that there were two small open reading frames (ORF) on each strand of the cloned DNA. In-frame fusion of ORFs to the reporter gene lacZ revealed that one ORF designated cre was indeed translated in vivo. The putative gene product deduced from the cre ORF is a basic and hydrophilic protein having a calculated molecular weight of 6 kdaltons.

A strain of Streptomyces nodosus (NPS007994) isolated from a marine sediment collected in Scripps Canyon, La Jolla, California, was found to produce lajollamycin (1), a nitro-tetraene spiro-beta-lactone-gamma-lactam antibiotic. The structure was established by complete analysis of spectroscopic data and comparison with known antibiotics oxazolomycin (2), 16-methyloxazolomycin (3), and triedimycin B (4). Lajollamycin (1) showed antimicrobial activity against both drug-sensitive and -resistant Gram-positive bacteria and inhibited the growth of B16-F10 tumor cells in vitro.