acid added to the medium in the above described culture method l amino acids of 5 mm l each described in table 1 below were used and the influence of the amino acids upon the fr901228 production was examined an amount of fr901228 in the culture solution was measured by high performance liquid chromatography column mightysil rp 18 gp particle size 3 u03bcm manufactured by kanto kagaku 3 0 mm i d u00d7 150 mm column temperature kept constant around 35 u00b0 c detection wavelength 210 nm flow rate 0 3 ml min injection amount 2 u03bcl mobile phase thf acetonitrile water phosphoric acid 570 380 50 1 the culture solution was centrifuged and the resulting strain was dried and the weight was measured thus an amount of dried strain was obtained and its amount with the respect to the culture solution was calculated as shown in table 1 a yield of fr901228 was increased through the addition of arginine arg histidine his or cysteine cys arginine and histidine also increased the amount of dried starin together with the addition but cysteine did not show change in the amount of dried strain as compared with the control accordingly the yield per dried strain amount.