Abstract A multi-enzyme route for the production of an atorvastatin side-chain was proposed. The approach includes the consecutive double aldol addition of acetaldehyde to the phenylacetamide amino-protected propanal by 2-deoxyribose- 5-phosphate aldolase (DERA), the oxidation by ketoreductase, the lipase-catalysed acylation and amino group deprotection by penicillin G-acylase. To explore the feasibility of the process, the DERA reaction was studied into detail. Based on the kinetic and stability studies, a mathematical model was developed and validated in a batch and fed-batch reactor. The highest productivity was obtained in repetitive batch reactor (229.1 g/(L day)). The highest final product concentration of 124 g/L was obtained in fed-batch reactor. The mathematical model-based optimisation provided insight into the possibilities for process metrics improvement. Further, the second step was explored. The results showed that the DERA reaction and the oxidation reaction can be carried out as the multi-enzyme one pot process in the sequential manner.

中文翻译：

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DERA催化双羟醛加成制备阿托伐他汀侧链前体的创新路线

摘要 提出了一种多酶途径生产阿托伐他汀侧链。该方法包括通过 2-脱氧核糖-5-磷酸醛缩酶 (DERA) 将乙醛连续双醛醇加成到苯乙酰胺氨基保护的丙醛、酮还原酶氧化、脂肪酶催化的酰化和青霉素 G-酰化酶的氨基脱保护。为了探索该过程的可行性，对DERA反应进行了详细研究。基于动力学和稳定性研究，在分批和补料分批反应器中开发和验证了数学模型。在重复间歇式反应器中获得最高生产率（229.1 g/（L 天））。在补料分批反应器中获得了 124 g/L 的最高最终产品浓度。基于数学模型的优化提供了对流程指标改进可能性的洞察。进一步探索了第二步。结果表明，DERA反应和氧化反应可以作为多酶一锅法依次进行。