This Small Business Innovation Research Phase I project is directed the use a combination of cross-linked enzyme crystal (CLEC(R)) technology and chemical modification to prepare a stable and active biocatalyst for antibiotic synthesis. Beta-lactam antibiotic manufacturing processes are comprised of multiple protection, deprotection and stoichiometric activation steps, generating 100 to 1000 fold more waste than product. Moreover, energy consumption is high since many of the steps must be performed at ultra-low temperatures. Altus Biologics is a world leader in biocatalysis; developing cross-linked enzyme crystal (CLEC(R)) technology for the stabilization of protein catalysts. Development of a form of Penicillin acylase that is active and stable in aqueous/organic solvent mixtures will allow the exploitation of the exquisite selectivity of this enzyme for catalyzing a one-step antibiotic coupling. Optimization of catalyst activity and stability in high concentrations of reactants and solvent mixtures will be performed through iterative chemical modification and cross-linking. Development of a stable and active biocatalyst will allow the economic manufacture of high-volume pharmaceuticals via an efficient and environ-mentally benign process.
