Carr Samuel C, O'Connor Sarah E
Department of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology, 07745 Jena, Germany.
Biochemistry. 2025 Jul 1;64(13):2712-2726. doi: 10.1021/acs.biochem.5c00234. Epub 2025 Jun 19.
Medium-chain dehydrogenases/reductases (MDRs) are enzymes that are well-known for catalyzing the reversible reduction of ketones or aldehydes or oxidation of alcohols. However, the biosynthetic pathways of the monoterpene indole alkaloids (MIAs), an important class of natural products derived from plants, highlight that MDRs can also catalyze 1,2- and 1,4-α,β-unsaturated iminium reductions, as well as 1,4-α,β-unsaturated carbonyl reduction. The noncanonical activities of these MDRs correlate with distinct catalytic architectures centered on amino acid substitutions that impact catalytic zinc coordination, acid/base catalysis, and proton relay. These noncanonical MDR catalytic architectures likely arose within the MDR subfamily of cinnamyl alcohol dehydrogenases (CADs). This review summarizes the currently characterized MIA biosynthetic MDRs along with an analysis of the catalytic mechanisms, structural underpinnings, and phylogeny.
中链脱氢酶/还原酶（MDRs）是一类以催化酮或醛的可逆还原反应或醇的氧化反应而闻名的酶。然而，单萜吲哚生物碱（MIAs）是一类重要的植物源天然产物，其生物合成途径表明，MDRs还可以催化1,2-和1,4-α,β-不饱和亚胺离子的还原反应，以及1,4-α,β-不饱和羰基的还原反应。这些MDRs的非经典活性与以氨基酸取代为中心的独特催化结构相关，这些取代影响催化锌配位、酸碱催化和质子传递。这些非经典的MDR催化结构可能起源于肉桂醇脱氢酶（CADs）的MDR亚家族。本综述总结了目前已表征的参与MIA生物合成的MDRs，并分析了其催化机制、结构基础和系统发育。
