SBIR Phase I: Development of a Stable, Heterogeneous Biocatalyst for Antibiotic Synthesis

这个小企业创新研究一期项目是直接使用交联酶晶体（CLEC(R)）技术和化学改性相结合来制备一种稳定和活性的抗生素合成生物催化剂。β -内酰胺类抗生素的生产过程由多个保护、去保护和化学计量激活步骤组成，产生的废物比产品多100至1000倍。此外，由于许多步骤必须在超低温下进行，因此能耗很高。Altus Biologics是生物催化领域的全球领导者；开发用于蛋白质催化剂稳定的交联酶晶体（CLEC(R)）技术。开发一种在水/有机溶剂混合物中具有活性和稳定性的青霉素酰化酶，将允许利用这种酶的精细选择性来催化一步抗生素偶联。通过反复的化学修饰和交联来优化催化剂在高浓度反应物和溶剂混合物中的活性和稳定性。一种稳定和活性的生物催化剂的发展将允许通过一种高效和环保的过程经济地制造大量药物。

9860988 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.