Schörken U, Sprenger G A
Institut für Biotechnologie 1, Forschungszentrum Jülich GmbH, P.O. Box 1913, D-52425 Jülich, Germany.
Biochim Biophys Acta. 1998 Jun 29;1385(2):229-43. doi: 10.1016/s0167-4838(98)00071-5.
Enzymes are increasingly being used to perform regio- and enantioselective reactions in chemoenzymatic syntheses. To utilize enzymes for unphysiological reactions and to yield novel products, a broad substrate spectrum is desirable. Thiamin diphosphate (ThDP)-dependent enzymes vary in their substrate tolerance from rather strict substrate specificity (phosphoketolases, glyoxylate carboligase) to more permissive enzymes (transketolase, dihydroxyacetone synthase, pyruvate decarboxylase) and therefore differ in their potential to be used as biocatalysts. We give an overview of the known substrate spectra of ThDP-dependent enzymes and present examples of multi-enzyme or chemoenzymatic approaches which involve ThDP-dependent enzymes as biocatalysts to obtain pharmaceutical compounds as ephedrine and glycosidase inhibitors, sex pheromones as exo-brevicomin, 13C-labeled metabolites, and other intermediates as 1-deoxyxylulose 5-phosphate, a precursor of vitamins and isoprenoids.
酶越来越多地用于化学酶促合成中的区域选择性和对映选择性反应。为了将酶用于非生理反应并产生新的产物，需要广泛的底物谱。硫胺素二磷酸（ThDP）依赖性酶的底物耐受性各不相同，从相当严格的底物特异性（磷酸酮醇酶、乙醛酸羧化酶）到更具宽容性的酶（转酮醇酶、二羟基丙酮合酶、丙酮酸脱羧酶），因此它们作为生物催化剂的潜力也不同。我们概述了ThDP依赖性酶的已知底物谱，并给出了多酶或化学酶促方法的实例，这些方法涉及使用ThDP依赖性酶作为生物催化剂来获得诸如麻黄碱和糖苷酶抑制剂等药物化合物、作为外-短叶松素的性信息素、13C标记的代谢物以及其他中间体，如1-脱氧木酮糖5-磷酸，它是维生素和类异戊二烯的前体。
