Cyclodipeptides from Metagenomic Library of a Japanese Marine Sponge

Culture-independent metagenomics is an attractive and promising approach to explore unique bioactive small molecules from marine sponges harboring uncultured symbiotic microbes. Therefore, we conducted functional screening of the metagenomic library constructed from the Japanese marine sponge Discodermia calyx. Bioassay-guided fractionation of plate culture extract of antibacterial clone pDC113 afforded eleven cyclodipeptides: Cyclo(L-Thr-L-Leu) (1), Cyclo(L-Val-D-Pro) (2), Cyclo(L-Ile-D-Pro) (3), Cyclo(L-Leu-L-Pro) (4), Cyclo(L-Val-L-Leu) (5), Cyclo(L-Leu-L-Ile) (6), Cyclo(L-Leu-L-Leu) (7), Cyclo(L-Phe-L-Tyr) (8), Cyclo(L-Trp-L-Pro) (9), Cyclo(L-Val-L-Trp) (10) and Cyclo(L-Ile-L-Trp) (11). To the best of our knowledge, these are first cyclodepeptides isolated from metagenomic library. Sequence analysis suggested that isolated cyclodipeptides were not synthesized by nonribosomal peptide synthetases and there was no significant indication of cyclodipeptide synthetases.