Tropinone reductase: A comprehensive review on its role as the key enzyme in tropane alkaloids biosynthesis

TAs, including hyoscyamine and scopolamine, were used to treat neuromuscular disorders ranging from nerve agent poisoning to Parkinson's disease. Tropinone reductase I (TR-I; EC 1.1.1.206) catalyzed the conversion of tropinone into tropine in the biosynthesis of TAs, directing the metabolic flow towards hyoscyamine and scopolamine. Tropinone reductase II (TR-II; EC 1.1.1.236) was responsible for the conversion of tropinone into pseudotropine, diverting the metabolic flux towards calystegine A3. The regulation of metabolite flow through both branches of the TAs pathway seemed to be influenced by the enzymatic activity of both enzymes and their accessibility to the precursor tropinone. The significant interest in the utilization of metabolic engineering for the efficient production of TAs has highlighted the importance of TRs as crucial enzymes that govern both the direction of metabolic flow and the yield of products. This review discussed recent advances for the TRs sources, properties, protein structure and biocatalytic mechanisms, and a detailed overview of its crucial role in the metabolism and synthesis of TAs was summarized. Furthermore, we conducted a detailed investigation into the evolutionary origins of these two TRs. A prospective analysis of potential challenges and applications of TRs was presented.