The fermentation production was enhanced by breeding a high-yield strain of daptomycin and optimizing the feeding process of the precursor substance.Experiments demonstrated that the high-yield strain DT-SR-18 was obtained via the atmospheric pressure room temperature plasma(ARTP)mutagenesis combined with streptomycin and rifampicin resistance breeding under a low-oxygen solution fermentation system.Compared to the original strain,the shaking flask fermentation production of DT-SR-18 increased by 36.2%.In a 50 L tank,the feeding process of sodium caprate as a precursor for daptomycin synthesis was optimized.Results showed that adding 25%sodium caprate solution at a constant rate of 0.5 mL/(h·L)over 24 hours led to a fermentation production of 2 351 μg/mL in a 500 L tank,significantly improving the yield of daptomycin.