Fluvirucins B7–B10, new antifungal macrolactams from a marine-derived Nonomuraea sp. MYH522

Abstract

Marine rare actinomycetes are an important source of secondary metabolites. From a marine-derived actinomycete Nonomuraea sp. MYH522, four new macrolactams, fluvirucins B₇–B₁₀, together with known fluvirucin B₆ were isolated. Their structures were determined based on comprehensive analysis of HRESIMS and NMR spectroscopic data as well as by comparing ¹³C 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 B₆–B₁₀ 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 B₆, B₉, and B₁₀ showed synergistic antifungal activity with fluconazole against fluconazole-resistant isolates of Candida albicans.