Fluvirucins B(7)–B(10), new antifungal macrolactams from a marine-derived Nonomuraea sp. MYH522

Marine rare actinomycetes are an important source of secondary metabolites. From a marine-derived actinomycete Nonomuraea sp. MYH522, four new macrolactams, fluvirucins B(7)–B(10), together with known fluvirucin B(6) were isolated. Their structures were determined based on comprehensive analysis of HRESIMS and NMR spectroscopic data as well as by comparing (13)C NMR resonances and optical rotation values with those for related congeners. Fluvirucins are characterized by a 14-membered macrolactam attached by an aminosugar moiety. The discovery of fluvirucins B(6)–B(10) enriched the N-acetylated derivatives of fluvirucins. The diverse alkyl substituents at C-2 and C-6 implied substrate promiscuity in fluvirucin polyketide biosynthesis. These compounds didn't exhibit any antibacterial or antifungal activities when used alone, which suggested the importance of the free amino group in the antimicrobial activity of fluvirucins. However, fluvirucins B(6), B(9), and B(10) showed synergistic antifungal activity with fluconazole against fluconazole-resistant isolates of Candida albicans.