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

SBIR 第一阶段：开发用于抗生素合成的稳定、多相生物催化剂

• 批准号: 9860988
• 负责人: James Lalonde
• 金额: $ 10万
• 依托单位: Altus Biologics Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9860988&HistoricalAwards=false
• 关键词: SBIR; Phase; Development; Stable; Heterogeneous

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.

9860988 该小企业创新研究第一阶段项目旨在使用交联酶晶体（CLEC（R））技术和化学修饰的组合来制备用于抗生素合成的稳定和活性生物催化剂。β-内酰胺抗生素的生产过程包括多个保护、脱保护和化学计量活化步骤，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，因此能耗高。Altus Biologics是生物催化领域的世界领导者;开发用于稳定蛋白质催化剂的交联酶晶体（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形式将允许利用这种酶的精确选择性来催化一步抗生素偶联。将通过反复的化学改性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。 开发一种稳定、活性的生物催化剂，将允许通过一种高效、无害的工艺经济地生产大量药物。