Penicillin conversion

Penicillin began the antibiotic revolution. Providing the first real weapon against microbial infections, penicillin (see ) first appeared to be a "magic bullet" that would cure all of man's ills. Infectious microbes soon developed resistance to penicillins, however. Great efforts in the pharmaceutical industry have focussed and still focus on the development of alternative antibiotics. One of the most useful families of agents is the cephalosporins (see FIG. ). The present invention provides a biological system for expanding the dethiazolidine ring of penicillins into the dehydrothiazine ring of cephalosporins or cephalosporin precursors. In particular, the invention defines reaction conditions under which expandase enzyme can convert penicillin substrates other than penicillin N into cephalosporins. The invention therefore provides a relatively inexpensive, uncomplicated, and environmentally friendly biological system for cephalosporin production from penicillins, which system can replace the synthetic chemical approaches currently utilized. In particular, the invention provides a system for producing DOAG and/or DAG, which can be enzymatically converted into 7-ADCA and 7-ADAC, which, in turn, can be enzymatically or chemically converted into valuable cephalosporins of commerce.