The Heat-Shock Metabolite Streptolactam D, Produced by High-Temperature Culture of 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 (), was isolated from the culture extract of thermotolerant sp. JA74. Production of compound 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 was determined by NMR and MS spectroscopic analyses, calculation of NMR and ECD spectra, and analysis of the biosynthetic gene cluster. Surprisingly, 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 localizes in the cell membrane and causes the cell to assume a short and thick morphology. Furthermore, is predicted to maintain cell membrane fluidity and impart thermotolerance to strain JA74, similar to cholesterol and saturated fatty acids. These data suggest that is produced to promote the survival of strain JA74 under high-temperature conditions.