IMMOBILIZED OXIDOREDUCTASE ENZYMES IN ORGANIC SYNTHESIS

有机合成中的固定化氧化还原酶

• 批准号: 2184595
• 负责人: JOHN P O'DALY
• 金额: $ 24.1万
• 依托单位: ALDERON BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2184595
• 关键词: alcohol dehydrogenase; bioreactors; catalyst; chemical synthesis; drug design /synthesis /production; gel; method development; nicotinamide adenine dinucleotide; nonwater solvent; organic chemicals; oxidoreductase; stereoisomer

DESCRIPTION: (Adapted from applicant's abstract) There is a need for new reagents for the production of optically pure pharmaceuticals. For this purpose, the investigators propose to develop for commercialization the new biphasic biocatalyst system for organic synthesis for which feasibility was successfully established in the Phase I work. The general objective is to develop the Phase I methodology in which cofactor dependent enzymes were used in organic solvents for the stereospecific production of high value compounds such as pharmaceuticals. The Phase I results demonstrated that horse liver alcohol dehydrogenase (HLADH), along with its cofactor nicotinamide adenine dinucleotide (NAD(H)), can be immobilized in a hydrogel, and operate in a bulk organic solvent to produce optically pure compounds from optically inactive precursors. The specific objective of Phase II will be to develop this new synthetic methodology into a general procedure for the low cost production of pharmaceutical and agricultural compounds using immobilized cofactor dependent oxido-reductase enzymes in organic solvents. The expected result is a commercially viable prototype immobilized oxido- reductase catalyst capable of operating in a bulk organic solvent. The three researchers submitting this proposal have collaborated successfully to establish the feasibility of an immobilized, cofactor-dependent, enzyme system for stereoselective hydrolysis and transesterification in organic solvent.

描述：(改编自申请者的摘要)需要新的 用于生产光学纯药物的试剂。为了这个 目的，调查人员建议开发用于商业化的 用于有机合成的新型两相生物催化剂体系 在第一阶段工作中成功地确定了可行性。这个 总体目标是开发第一阶段方法，在该方法中 辅酶依赖酶在有机溶剂中用于 立体定向生产高价值化合物，如 制药公司。 一期实验结果表明，马肝醇脱氢酶 和它的辅因子烟酰胺腺嘌呤二核苷酸 (NAD(H))，可固定在水凝胶中，并可散装操作 有机溶剂用于从光学材料中生产光学纯化合物 不活跃的前驱物质。第二阶段的具体目标将是 将这一新的综合方法论发展为一种通用的程序 低成本生产药物和农用化合物 有机材料中固定化辅因子依赖氧化还原酶 溶剂。 预期的结果是一种商业上可行的固定化氧化- 能够在大量有机溶剂中工作的还原酶催化剂。这个 提交这项提案的三名研究人员已成功合作 为了确定一种固定化的、依赖辅因子的 用于立体选择性水解和酯交换的酶系统 有机溶剂。