Accellular synthesis of cephalosporins
AssigneeMassachusetts Institute of Technology
InventorsArnold L. Demain, Masanobu Kohsaka
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Abstract
A cephalosporin antibiotic is produced from a precursor comprising the five membered thiazolidine ring and the .beta. lactam moiety characteristics of penicillins by contacting the precursor with a cell-free extract of Cephalosporium acremonium in the presence of ATP under conditions favoring high oxygen transfer. Preferably, an ATP regeneration system comprising a phosphate donor and a phosphotransferase enzyme is included in the reaction.
Claims10
A process for producing a cephalosporin antibiotic, said process comprising the steps of:
- providing a cell-free extract of Cephalosporium acremonium;
- providing a source of starting material comprising a substance having the formula:
- ##STR7## wherein R is a hydrocarbon containing 1-4 carbon atoms terminally substituted with a radical selected from the group consisting of carboxy, amino, and combinations thereof;
- contacting the extract and the starting material in a reaction zone while promoting oxygen transfer;
- providing ATP as an energy source to said reaction zone;
- and
- allowing a component of the extract to react with said precursor for a sufficient amount of time to produce a cephalosporin antibiotic.
A process for producing a cephalosporin antibiotic, said process comprising the steps of:
- providing a source of Cephalosporium acremonium mycelia;
- treating said mycelia with lytic enzyme endo.beta.(1.fwdarw.3) glucanse, endo.beta.(1.fwdarw.4) glucanse and, from Arthrobacter, zymolyase;
- incubating the treated mycelia to produce a protoplast suspension and homogenizing the suspension to produce a cell free extract;
- providing a source of starting material selected from the group consisting of:
- ##STR11## wherein R is:
- --(CH.sub.2).sub.3 --COOH ##STR12## contacting the extract and the starting material in the presence of ATP in a reaction zone while promoting oxygen transfer;
- and allowing a component of the extract to react with the starting material for a sufficient amount of time to produce a cephalosporin antibiotic.
Dependencies are inferred from the claim text.