Bioscience Evidence 2024, Vol.14, No.2, 39-43 http://bioscipublisher.com/index.php/be 39 Scientific Review Open Access Exploring the Role of Plant Carbonic Anhydrase-like Enzymes in the Synthesis of Neuroactive Alkaloids ManmanLi Hainan Institute of Tropical Agricultural Resources, Sanya, 572024, China Corresponding author email: lmm314.editor@gmail.com Bioscience Evidence, 2024, Vol.14, No.2 doi: 10.5376/be.2024.14.0006 Received: 18 Jan., 2024 Accepted: 23 Feb., 2024 Published: 07 Mar., 2024 Copyright © 2024 Li, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Li M.M., 2024, Exploring the role of plant carbonic anhydrase-like enzymes in the synthesis of neuroactive alkaloids, Bioscience Evidence, 14(2): 39-43 (doi: 10.5376/be.2024.14.0006) The paper titled "Role of Plant Carbonic Anhydrase-Like Enzymes in Neuroactive Alkaloid Biosynthesis" published in the journal Nature on November 8, 2023, by authors Ryan S. Nett, Yaereen Dho, Chun Tsai, among others, from the Department of Chemical Engineering at Stanford University, the Howard Hughes Medical Institute, and the Department of Molecular and Cellular Biology at Harvard University, etc. This study focuses on a class of plant carbonic anhydrase-like enzymes (CALs) that play a key role in the biosynthesis of neuroactive alkaloids in gymnosperms. Through in-depth analysis of the biosynthetic pathways in ferns, the research team revealed how these CAL proteins participate in the generation of neuroactive gymnosperm alkaloids, such as huperzine A, through a series of complex enzyme-catalyzed reactions. This work not only expands our understanding of plant-specific metabolic pathways but also provides a new perspective for the future discovery and development of plant alkaloid-based medications. 1 Experimental Data Analysis The CAL proteins identified in the study participate in the formation of polycyclic structures by catalyzing a series of Mannich-type condensation reactions. The experimental data show that this process is crucial for the generation of precursors to alkaloids like huperzine A. Furthermore, through transcriptomic and co-expression analyses, the research team successfully identified genes highly correlated with the expression patterns of these CAL proteins in ferns, providing important clues for further understanding the functions and regulatory mechanisms of CAL proteins. Figure 1 presents the study of unknown steps in lycopodium alkaloid biosynthesis in lycophyte plants. Figure 1a describes a series of unknown chemical transformations that convert early precursors into a diversified lycopodium alkaloid scaffold. The red and blue structures represent visual representations of the main structural categories of lycopodium alkaloids, not actual compounds found in nature. The box displays representative lycopodium alkaloids, including the cholinesterase inhibitor HupA. Figure 1b illustrates the identification process of new biosynthetic enzyme candidates guided by transcriptomic information, where c.p.m. stands for counts per million. This demonstrates the interdisciplinary approach adopted in studying the alkaloid synthesis mechanisms in lycophyte plants, incorporating both chemical and bioinformatics methods. Figure 2 illustrates the stepwise discovery of enzymes contributing to compound skeleton formation in the early biosynthetic pathway. The extracted ion chromatograms (EIC) for the assumed intermediates' corresponding m/z values were revealed by transiently co-expressing candidate biosynthetic genes from P. tetrastichus in N. benthamiana (indicated by blue boxes). Generally, compounds appear in the form of [M+H]+ ions. For compound 9, the originating fragment m/z 164.1434 ([M-C5H9N+H]+) served as the primary detection ion, thus used as the diagnostic marker for this compound. All compounds were detected using LC-MS with an HILIC column, except for the enantiomer of 6, which was observed using a C18 column. Note that the y-axis for each set of chromatograms is on different scales, but the scale within an EIC chart is constant. The black arrows indicate the
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