Introduction of Radioactive Sulfur (S 35 ) Into the Penicillin Molecule by Biosynthesis

Abstract

Radioactive penicillin was produced by surface growth of Penicillium notatum NRRL 1249 B 21, on a medium containing radioactive S as Na2SO4. The S available in 272 1. of the medium was 16.475 g. of S32 and 0.528[gamma], or 24.2 mc. of S36 as inorg. sulfates. The ratio of S35 to S32 was 3.12 X 10-8 in the original medium. The mold was harvested 10 days after inoculation of the medium and the amorphous or crude penicillin extracted. The yield was 53.31 g. with an antibiotic activity of 2.47 X 105 [mu]./g. and a specific radioactivity of 15.56 [mu] c/gm. Hence, 3.4% of the original radioactivity was in the amorphous penicillin. A part was purified. In one run, a 24-tube transfer study was made with 508 mg. Most was type G with a little F and dihydro F. The yields of crystalline triethylamine G and the corresponding amorphous penicillin were assayed, giving the following % recoveries going from the amorphous to the crystalline material: weight, 8.1; U.,27; S32, 31.1; S36, 31.9. Hence, the radioactive S was incorporated into penicillin, and all the S in the amorphous penicillin was present in the penicillin molecule. The ratio of S35 to S32 was 3.04 X 10-8. The radioactive S apparently behaves like ordinary S in the biosynthesis.