Non-cytotoxic Antifungal Agents: Isolation and Structures of Gageopeptides A–D from a <i>Bacillus</i> Strain 109GGC020

Antifungal resistance and toxicity problems of conventional fungicides highlighted the requirement of search for new safe antifungal agents. To comply with the requirement, we discovered four new non-cytotoxic lipopeptides, gageopeptides A–D, <b>1–4,</b> from a marine-derived bacterium <i>Bacillus subtilis</i>. The structures and stereochemistry of gageopeptides were determined by NMR data analysis and chemical means. Gageopeptides exhibited significant antifungal activities against pathogenic fungi <i>Rhizoctonia solani</i>, <i>Botrytis cinerea</i>, and <i>Colletotrichum acutatum</i> with minimum inhibitory concentration (MIC) values of 0.02–0.06 μM. In addition, these lipopeptides showed significant motility inhibition and lytic activities against zoospores of the late blight pathogen <i>Phytophthora capsici</i>. These compounds also showed potent antimicrobial activity against Gram positive and Gram negative bacteria with MIC values of 0.04–0.08 μM. However, gageopeptides A–D did not exhibit any cytotoxicity (GI₅₀ > 25 μM) against cancer cell lines in sulforhodamine B (SRB), 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), and WST-1 ((4-[3–4-iodophenyl]-2-(4-nitrophenyl)-2<i>H</i>-5-tetrazolio)-1,3-benzene disulfonate)) assays, demonstrating that these compounds could be promising candidates for the development of non-cytotoxic antifungal agents