Lydicamycin

In screening for anti-MRSA antibiotics, novel lydicamycin congeners, TPU-0037-A, B, C and D, were isolated from a culture broth of an actinomycete strain. The producing strain, TP-A0598, was isolated from a seawater sample collected in Toyama Bay, Japan, and identified as Streptomyces platensis based on taxonomic characteristics. TPU-0037-A, B, C and D were purified by HP-20 resin, ODS column chromatographies and preparative HPLC, consecutively, and their structures were determined to be 30-demethyllydicamycin, 14,15-dehydro-8-deoxylydicamycin, 30-demethyl-8-deoxylydicamycin and 8-deoxylydicamycin, respectively, by NMR and MS analyses. The new congeners showed antibiotic activity against gram-positive bacteria including MRSA with the MIC of 1.56 to approximately 12.5 microg/ml.

The structure of a new antibiotic designated lydicamycin was elucidated as shown in Fig. 1 by NMR spectral analysis including a variety of 2D techniques. Lydicamycin possesses a novel skeleton containing tetramic acid and amidinopyrrolidine moieties.

Streptomyces sp. TP-A0598, isolated from seawater, produces lydicamycin, structurally unique type I polyketide bearing two nitrogen-containing five-membered rings, and four congeners TPU-0037-A, -B, -C, and -D. We herein report the 8 Mb draft genome sequence of this strain, together with classification and features of the organism and generation, annotation and analysis of the genome sequence. The genome encodes 7,240 putative ORFs, of which 4,450 ORFs were assigned with COG categories. Also, 66 tRNA genes and one rRNA operon were identified. The genome contains eight gene clusters involved in the production of polyketides and nonribosomal peptides. Among them, a PKS/NRPS gene cluster was assigned to be responsible for lydicamycin biosynthesis and a plausible biosynthetic pathway was proposed on the basis of gene function prediction. This genome sequence data will facilitate to probe the potential of secondary metabolism in marine-derived Streptomyces.