Abstract
Background
Secondary metabolites such as benzylisoquinoline alkaloids (BIA) have attracted considerable attention because of their pharmacological properties and potential therapeutic applications. Methyltransferases (MTs) can add methyl groups to alkaloid molecules, altering their physicochemical properties and bioactivity, stability, solubility, and recognition by other cellular components. Five types of O-methyltransferases and two types of N-methyltransferases are involved in BIA biosynthesis.
Objective
Since MTs may be the source for the discovery and development of novel biomedical, agricultural, and industrial compounds, we performed extensive molecular and phylogenetic analyses of O- and N-methyltransferases in BIA-producing plants.
Methods
MTs involved in BIA biosynthesis were isolated from transcriptomes of Berberis koreana and Caulophyllum robustum. We also mined the methyltransferases of Coptis japonica, Papaver somniferum, and Nelumbo nucifera from the National Center for Biotechnology Information protein database. Then, we analyzed the functional motifs and phylogenetic analysis.
Result
We mined 42 O-methyltransferases and 8 N-methyltransferases from the five BIA-producing plants. Functional motifs for S-adenosyl-L-methionine-dependent methyltransferases were retained in most methyltransferases, except for the three O-methyltransferases from N. nucifera. Phylogenetic analysis revealed that the methyltransferases were grouped into four clades, I, II, III and IV. The clustering patterns in the phylogenetic analysis suggested a monophyletic origin of methyltransferases and gene duplication within species. The coexistence of different O-methyltransferases in the deep branch subclade might support some cases of substrate promiscuity.
Conclusions
Methyltransferases may be a source for the discovery and development of novel biomedical, agricultural, and industrial compounds. Our results contribute to further understanding of their structure and reaction mechanisms, which will require future functional studies.
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(Modified from Hagel et al. (2015)). Abbreviation: 3'-OHase, 3'-hydroxylase; 3'OMT, 3'-O-methyltransferase; 4HPPDC, 4-hydroxyphenylpyruvate decarboxylase; 4'OMT, 3'-hydroxyl-N-methylcoclaaurine 4'-O-methyltransferase; 6OMT, nocolaurine 6-O-methyltransferase, AT1, 1,13-dihydroxy-N-methycanadine 13-O-acetyltransferase; BBE, berberine bridge enzyme; BS, berbamunine synthase; CAS, canadine synthase; CNMT, coclaurine N-methyltransferase; CODN, codein O-demethylase; CoOMT, columbamine O-methyltransferase; COR, codeinone reductase; CTS, corytuberine synthase; CYP82X1, 1-hydroxyl-13-O-acetyl-N-methetylcanadine 8-hydroxylase; CYP82X2, 1-hydroxyl-N-methylcanadine 13-dehydroxylase; CYP82Y1, N-methylcanadine 1-hydroxylase; CDBOX, dihydrobenzophenanthridine oxidase; CXE, 3-O-acetypapaveroxine carboxylase; DBOX, dihydrobenzophenathridine oxidase; LdM, laudanisine demethylase; MSH, N-methylstylopine hydroxylase; N7OMT, norreticuline 7-O-methyltransferase; NCS, norcoclaurine synthase; NMCanH,N-methylcanadine 1-hydroxylase; NMCH, N-methylcocaurine 3'hydroxylase; NOS, noscapine synthase; P6H, protopine 6-hydroxylase; REPI, reticuline epimerase; SalAT, salutaridiol 7-O-acetyltransferase; SalR, salutaridine reductase; SalSyn, salutaridine synthase; SanR, Sanguinarine reductase; SOMT, scoulerine 9-O-methy;transferase; SPS, stylopine synthase; STOX, (S)-tetrahydroprotoberberine oxidase; T6ODM, thebaine 6-O-demethylase; TNMT, tetrahydroprotoberberine N-methyltransferase; TYDC, tyrosine decarboxylase; TyrAT, tyrosine aminotransferase
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Acknowledgements
This work was supported by the National Institute of Biological Resources (NIBR202322101).
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I.-Y.C. and S.L. conceived and designed the project and edited the manuscript. B.-S.C. and N.-S.K. contributed to the data analysis and drafted the manuscript. N.-I.P., Y.P., K.-C.P., E.S.K. and Y.K.S. prepared the sample materials and conducted an experiment of substance content. All authors have read and agreed to the published version of the manuscript.
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Lee, S., Park, NI., Park, Y. et al. O- and N-Methyltransferases in benzylisoquinoline alkaloid producing plants. Genes Genom 46, 367–378 (2024). https://doi.org/10.1007/s13258-023-01477-4
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DOI: https://doi.org/10.1007/s13258-023-01477-4