RIT 2214, a new biosynthetic penicillin produced by a mutant of Cephalosporium acremonium.
A number of lysine-requiring auxotrophs of Cephalosporium acremonium were investigated for incorporation of side-chain precursors and for accumulation of beta-lactam compounds. One of the auxotrophs, Acremonium chrysogenum ATCC 20389, producing cephalosporin C and penicillin N only if grown in media supplemented with DL-alpha-amino-adipic acid (DL-alpha-AAA), was found to use L-S-carboxymethylcysteine (L-CMC) as a side-chain precursor for the synthesis of a new penicillin (RIT 2214). No corresponding cephalosporin was detected. The penicillin present in the culture filtrate, was concentrated by adsorption on activated carbon and successive column chromatography on Amberlite IRA-68 and Amberlite XAD-4. Final purification was achieved by cellulose column chromatography. RIT 2214 was identified as 6-(D)-[(2-amino-2-carboxy)-ethylthio]-acetamido]-penicillanic acid by spectral analysis, bioactivity spectrum, elucidation of side-chain structure and finally by semisynthesis. Its biological properties were also evaluated.
D015074:2-Aminoadipic Acid / Q000378:metabolism; D000164:Acremonium / Q000378:metabolism*; D000818:Animals; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000517:prevention & control; D002233:Carbocysteine / Q000378:metabolism; D002511:Cephalosporins / Q000096:biosynthesis; D055598:Chemical Phenomena; D002621:Chemistry; D004355:Drug Stability; D005285:Fermentation; D007769:Lactams / Q000096:biosynthesis; D008239:Lysine / Q000378:metabolism; D051379:Mice; D010406:Penicillins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D013997:Time Factors
D002511:Cephalosporins; D007769:Lactams; D010406:Penicillins; D015074:2-Aminoadipic Acid; D002233:Carbocysteine; D008239:Lysine