The kinetics of enzymatic aldol reaction catalyzed by DERA (2-deoxyribose-5-phosphate aldolase) was studied. The reaction between acetyloxyacetaldehyde/acetaldehyde and chloroacetaldehyde/acetaldehyde in the presence of DERA produces chiral lactol intermediates, which are useful in the synthesis of optically pure super-statins. The experimental approach was designed studying batch and fed-batch reaction conditions adding different amounts of applied reactants. A three-step kinetic model was proposed including the formation of the intermediate product, synthesis of the main desired product and the synthesis of the side product by parallel non-desired secondary reaction. The kinetics of enzyme inactivation caused by reactants was also included in kinetic model design. The establishment of the kinetic model based on the two-substrates binding assuming random mechanism. After the development of the kinetic model, kinetic parameters were determined by non-linear least squares approximation search method, until the minimal differences between experimental and calculated data were achieved. The highest concentrations of the desired main product were produced in the case of fed-batch experiments applying such feeding regime that minimal surplus of reactants in the reaction mixture was attained, which consequently led to lower losses in the enzyme activity. Obtained kinetic parameters showed similar value of inactivation constant for acetyloxyacetaldehyde and acetaldehyde, whereas in the case of chloroacetaldehyde the number was significantly higher. To our knowledge, this is the first developed kinetic model describing the DERA catalyzed reaction of 2-substituted acetaldehydes to corresponding lactols. Obtained kinetic model can be used in further reactor design in the manner of optimizing the process by lowering the loss of enzyme activity in order to achieve higher amounts of the desired main product.

研究了DERA（2-脱氧核糖-5-磷酸醛缩酶）催化的醛缩酶反应动力学。在DERA存在下，乙酰氧基乙醛/乙醛和氯乙醛/乙醛之间的反应产生手性内酯中间体，可用于合成光学纯的超级他汀类药物。设计了实验方法来研究分批和分批进料的反应条件，并添加了不同量的反应物。提出了三步动力学模型，包括中间产物的形成，主要所需产物的合成以及通过平行的不希望的次级反应的副产物的合成。由反应物引起的酶失活的动力学也包括在动力学模型设计中。在假设随机机制的情况下，基于两种底物结合的动力学模型的建立。建立动力学模型后，通过非线性最小二乘近似搜索法确定动力学参数，直到获得实验数据与计算数据之间的最小差异。在采用这种进料方式的分批进料实验的情况下，产生了最高浓度的所需主要产物，从而使反应混合物中反应物的剩余量达到最小，从而降低了酶活性的损失。所获得的动力学参数显示乙酰氧基乙醛和乙醛的失活常数值相似，而在氯乙醛的情况下，该数目明显更高。据我们所知，这是第一个开发的动力学模型，描述了DERA催化2-取代的乙醛与相应的乳糖醇反应。所获得的动力学模型可以通过降低酶活性的损失来优化过程的方式，用于进一步的反应器设计中，从而获得更高数量的所需主产物。