To improve the production of heme by leghemoglobin in Saccharomyces cerevisiae,the concentration of heme in fermentation liquid was taken as the index,and the response surface method was adopted on the basis of a single factor test,with the addition of 5-aminolevulinic acid,fermentation time,and fermentation temperature as the influencing factors.The quadratic regression equation was established with the concentration of heme in fermentation solution as the response value,and the optimal combination was obtained by response surface analysis.The results showed that the content of 5-aminolevulinic acid had the greatest effect on the heme concentration,followed by fermentation temperature,and finally fermentation time.Considering factors such as time,energy consumption,and yield:when the pH value of fermentation medium was 5,ferric sulfate and 5-aminolevulinic acid were added to the fermentation medium to the final concentration of 10 μmol/L and 1.35 mmol/L,respectively,the concentration of inducer galactose was 80 g/L,the fermentation temperature was 28 ℃,and the fermentation time was 50 h,the fermentation effect was better.Under this optimized condition,the heme concentration was increased to 9.036 μmol/L,and a high yield was obtained.Further optimization could lead to a promising industrialization scenario.