THE USE OF STABILIZED PENICILLIN ACYLASE DERIVATIVES IMPROVES THE DESIGN OF KINETICALLY CONTROLLED SYNTHESIS

The advantages of the use of stabilised derivatives in the kinetically controlled synthesis catalysed by penicillin G acylase has been discu ssed. Stabilised derivatives were found to be less inhibited by the nu cleophile than non-stabilised ones, improving in that way the reaction rate. Also, more resistance under unfavourable conditions (e.g. prese nce of methanol) was found using stabilised derivatives. Multipoint co valently attached derivatives prepared in the presence of penicillin s ulfoxide showed the same hydrolytic/synthetic ratio as the non-distort ed enzyme suggesting that the stabilisation strategy is able to increa se the enzyme rigidity without promoting significant changes in the en zyme properties. In addition, the effect of the enzyme source was foun d to be significant: enzyme derivatives from Escherichia coli appeared to have better properties as catalysts of these reactions than enzyme derivatives of penicillin G acylase from Kluivera citrophila.