LOW-MOLECULAR-WEIGHT THIOLS IN STREPTOMYCETES AND THEIR POTENTIAL ROLE AS ANTIOXIDANTS

The intracellular low-molecular-weight thiols present in five gram-pos itive Streptomyces species and one Flavobacterium species were analyze d by high-performance liquid chromatography after fluorescence labelin g with monobromobimane. Bacteria were chosen to include penicillin and cephalosporin beta-lactam producers and nonproducers. No significant amount of glutathione was found in any of the streptomycetes. Major in tracellular thiols in all strains examined were cysteine, coenzyme A, sulfide, thiosulfate, and an unknown thiol designated U17. nose strept omycetes that make beta-lactam antibiotics also produce significant am ounts of delta-(L-alpha-aminoadipyl)-L-Cysteinyl-D-valine (ACV), a key intermediate in their biosynthesis. In Streptomyces clavuligerus, a p otent producer of beta-lactams, the level of ACV was low during the ea rly phase of growth and increased rapidly toward the end of exponentia l growth, paralleling that of antibiotic production. These and other o bservations indicate that ACV does not function as a protective thiol in streptomycetes. U17 may have this role since it was the major thiol in all streptomycetes and appeared to occur at levels about 10-fold h igher than those of the other thiols measured, including ACV. Purifica tion and amino acid analysis of U17 indicated that it contains cystein e and an unusual amine that is not one of the common amino acids. This thiol is identical to an unknown thiol found previously in Micrococcu s roseus and Streptomyces griseus. A high level of ergothioneine was f ound in Streptomyces lactamdurans, and several unidentified thiols wer e detected in this and other streptomycetes.