Statins are a group of drugs used for lowering cholesterol levels in the human bloodstream to prevent cardiovascular diseases and its synthesis is a challenge because of chemical and stereochemical requirements. In this work, a multi-enzyme one-pot sequential strategy was employed to obtain lactonized statin side-chain precursor and was compared to the two-pot process. The enzymatic production of this valuable product is rarely examined comparing to the traditional chemical methods. The examined cascade consisted of two consecutive reactions: lactol production by the 2-deoxyribose-5-phosphate aldolase (DERA)-catalysed double aldol addition of acetaldehyde and chloroacetaldehyde and its oxidation by the NAD-dependent aldehyde dehydrogenase (AlDH). NADH oxidase (NOX) was employed for the coenzyme regeneration. The insight in all reactions of the system was performed by enzyme kinetic and stability studies. Based on these data the mathematical models were developed and validated in a batch reactor. The oxidation was carried out using both purified (two-pot) and crude lactol (one-pot) obtained in the DERA-catalysed reaction. Better process metrics and greater stability of the AlDH was observed in one-pot system, thus demonstrating an additional benefit in favor of running multi-enzymatic (cascade) processes.

他汀类药物是用于降低人类血液中胆固醇水平以预防心血管疾病的一组药物，由于化学和立体化学方面的要求，他汀类药物的合成是一项挑战。在这项工作中，采用了一种多酶一锅顺序策略来获得内酯化他汀类药物侧链前体，并与两锅法进行了比较。与传统的化学方法相比，很少检查这种有价值的产品的酶促生产。所检查的级联包括两个连续的反应：由2-脱氧核糖-5-磷酸醛缩酶（DERA）催化的乙醛和氯乙醛的双醛醇加成生成的内酰胺，以及NAD依赖性醛脱氢酶（AlDH）对其的氧化。将NADH氧化酶（NOX）用于辅酶再生。通过酶动力学和稳定性研究来了解系统的所有反应。基于这些数据，在间歇反应器中开发并验证了数学模型。使用在DERA催化的反应中获得的纯化的（两锅）和粗制的乳醇（一锅）两者进行氧化。在一锅系统中观察到更好的工艺指标和AlDH的更大稳定性，因此证明了有利于运行多酶（级联）工艺的其他好处。