Institute of Biological Chemistry, Washington State University, Pullman, WA 99164, U.S.A.
Department of Chemistry, Washington State University, WA 99164.
Biochem J. 2020 Jun 12;477(11):2027-2038. doi: 10.1042/BCJ20200174.
Alkenes and ketones are two classes of ubiquitous, toxic organic compounds in natural environments produced in several biological and anthropogenic processes. In spite of their toxicity, these compounds are utilized as primary carbon and energy sources or are generated as intermediate metabolites in the metabolism of other compounds by many diverse bacteria. The aerobic metabolism of some of the smallest and most volatile of these compounds (propylene, acetone, isopropanol) involves novel carboxylation reactions resulting in a common product acetoacetate. Propylene is metabolized in a four-step pathway involving five enzymes where the penultimate step is a carboxylation reaction catalyzed by a unique disulfide oxidoreductase that couples reductive cleavage of a thioether linkage with carboxylation to produce acetoacetate. The carboxylation of isopropanol begins with conversion to acetone via an alcohol dehydrogenase. Acetone is converted to acetoacetate in a single step by an acetone carboxylase which couples the hydrolysis of MgATP to the activation of both acetone and bicarbonate, generating highly reactive intermediates that are condensed into acetoacetate at a Mn2+ containing the active site. Acetoacetate is then utilized in central metabolism where it is readily converted to acetyl-coenzyme A and subsequently converted into biomass or utilized in energy metabolism via the tricarboxylic acid cycle. This review summarizes recent structural and biochemical findings that have contributed significant insights into the mechanism of these two unique carboxylating enzymes.
烯烃和酮类是两种在自然环境中普遍存在的有毒有机化合物，它们在多种生物和人为过程中产生。尽管这些化合物具有毒性，但许多不同的细菌将它们用作主要的碳和能源来源，或者将它们作为其他化合物代谢的中间代谢物生成。一些最小和最易挥发的这些化合物（丙烯、丙酮、异丙醇）的需氧代谢涉及新颖的羧化反应，导致共同产物乙酰乙酸盐。丙烯通过涉及五种酶的四步途径代谢，其中最后一步是由独特的二硫键氧化还原酶催化的羧化反应，该酶将硫醚键的还原裂解与羧化偶联起来，产生乙酰乙酸盐。异丙醇的羧化作用始于通过醇脱氢酶转化为丙酮。丙酮在一步中被丙酮羧化酶转化为乙酰乙酸盐，该酶将 MgATP 的水解与丙酮和碳酸氢盐的激活偶联起来，生成高度反应性的中间体，在含有活性位点的 Mn2+ 上缩合成乙酰乙酸盐。然后，乙酰乙酸盐在中心代谢中被利用，它很容易转化为乙酰辅酶 A，随后通过三羧酸循环转化为生物质或在能量代谢中被利用。本综述总结了最近的结构和生化发现，这些发现为这两种独特的羧化酶的机制提供了重要的见解。
