Lipases have emerged from their metabolic use in ester cleavage of triglycerides to versatile biocatalysts that can be used for enantioselective hydrolysis of esters in water and for transesterification and transformation of esters to amides in organic solvents. 1 In addition, during the last 10 years, enzymes have also proven to be effective catalysts for polymerization reactions that proceed cost effectively with high regio-, enantio-, and chemoselectivity under relatively mild conditions. 2,3 In this respect, Candida antarctica lipase B (CALB) immobilized on polyacrylic resin (Novozyme 435) is a particularly useful enzyme preparation because it shows exceptionally high stability and good activity in organic solvents, even at higher temperatures. Although CALB has successfully been employed for the synthesis of polyesters from linear 4-8 and cyclic 9-15 starting materials, little has been reported on the preparation of polyamides catalyzed by enzymes. 16,17 Schwab et al. have recently described the first approach for a synthesis of unbranched poly(β-alanine), nylon 3, by enzymatic ring-opening polymerization starting from unsubstituted β-lactam (2-azetidinone, β-propiolactam). 18 The polymerization, however, proceeds with poor yield and with a maximum chain length of only 18 units and an average length of 8. Therefore, an optimization of the process is still necessary to produce a polymer for industrial use. This is, indeed, desirable because it

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Enzymatic polymerization has emerged over the last 5 years as a field of considerable interest and commercial promise. The reaction proceeds with high regio-, enantio-, and chemoselectivity under relatively mild conditions. Enzymes have been used so far to synthesize polyesters, polysaccharides, polycarbonates, polyphenols, polyanilines, vinyl polymers, and poly-amino acids [1]. Particularly, lipase B of Candida antarctica immobilized on polyacrylic resin (Novozyme 435) has proven to be a very versatile catalyst and has successfully been used for the synthesis of polyesters from various substrates [2][3] [4]. Little, however, has been reported on the enzyme catalyzed synthesis of polyamides [5].While it has been shown that nylons can chemically be produced from the corresponding amino acids or by anionic ring-opening polymerization of 5-13 membered unsubstituted lactams, poly-β-alanine has not yet been obtained by either polymerization of β-alanine or β-lactam (2-azetidinone). Using lipase B of Candida antarctica we have recently been successful in the production of unbranched poly-βalanine starting from unsubstituted β-lactam [6].Here we report preliminary molecular modeling studies of the lipase catalyzed ringopening polymerization of β-lactam towards an understanding of the underlying enzymatic mechanism. We can show that amide formation initially follows the well-known enzymatic acylation of Ser105 by β-lactam using Asp187 and His224 of the catalytic centre and Thr40 and Gly106 as oxy-anion hole. The elongation of the chain, however, utilizes different parts of the active site. The mechanism is only applicable for β-lactam and can not be utilized by β-alanine and suggests a reasoning for the experimental finding that β-alanine can not be polymerized enzymatically but rather inhibits the polymerization in a copolymerization experiment with β-lactam and β-alanine.