The Heat-Shock Metabolite Streptolactam D, Produced by High-Temperature Culture of Streptomyces sp. JA74, Promotes Thermotolerance via Self-Membrane Stabilization

A new streptolactam derivative featuring a 4-membered ring fused to a 6-membered ring in the macrolactam structure, streptolactam D (1), was isolated from the culture extract of thermotolerant Streptomyces sp. JA74. Production of compound 1 increased with high-temperature cultivation, and this type of compound was previously designated as a "heat-shock metabolite (HSM)" by our research group. The structure of 1 was determined by NMR and MS spectroscopic analyses, calculation of NMR and ECD spectra, and analysis of the biosynthetic gene cluster. Surprisingly, 1 promoted the growth of strain JA74 under high-temperature conditions and increased the growth limit temperature. Analysis of the mode of action using ultracentrifugation and scanning electron microscopy suggested that 1 localizes in the cell membrane and causes the cell to assume a short and thick morphology. Furthermore, 1 is predicted to maintain cell membrane fluidity and impart thermotolerance to strain JA74, similar to cholesterol and saturated fatty acids. These data suggest that 1 is produced to promote the survival of strain JA74 under high-temperature conditions.