Reference: Zhang Q, et al. (2025) Functional Characterization of GNA1 as a Serotonin N-Acetyltransferase Reveals a Key Role in the Serotonin to Melatonin Pathway in Saccharomyces cerevisiae. J Pineal Res 77(4):e70065

Reference Help

Abstract


Melatonin (N-acetyl-5-methoxytryptamine) is an evolutionarily conserved molecule with diverse physiological functions across prokaryotes, plants, and animals, including circadian rhythms regulation in animals and developmental modulation in plants. Although the biosynthetic pathways of melatonin have been well elucidated in mammals and plants, the enzymatic mechanisms underlying microbial melatonin synthesis remain largely unexplored. Saccharomyces cerevisiae, a genetically tractable eukaryotic model, provides a valuable system for elucidating fungal melatonin biosynthesis. In this study, we identified the GNA1 gene as a potential serotonin N-acetyltransferase candidate in S. cerevisiae through genome-wide comparative analysis. The GNA1 protein was heterologously expressed in Escherichia coli BL21(DE3), purified, and subjected to detailed enzymatic characterization. In vitro assays revealed that GNA1 exhibits acetyltransferase activity toward both serotonin and 5-methoxytryptamine (5-MT), with maximal catalytic efficiency observed at 30°C and pH 8.5. Substrate specificity and kinetic analyses demonstrated a pronounced preference for 5-MT, supporting a biosynthetic route in which serotonin undergoes O-methylation before acetylation by GNA1 to yield melatonin. This study provides the first biochemical evidence linking GNA1 to melatonin biosynthetic pathway in yeast and offers new insights into microbial melatonin biosynthesis, highlighting its potential evolutionary and metabolic significance.

Reference Type
Journal Article
Authors
Zhang Q, Cheng D, Tang X, Li Y, Han N, Xu W, Ding J
Primary Lit For
Additional Lit For
Review For

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene/Complex Qualifier Gene Ontology Term Aspect Annotation Extension Evidence Method Source Assigned On Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Disease Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Disease Ontology Term Qualifier Evidence Method Source Assigned On Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, or SPELL.

Regulator Target Direction Regulation Of Happens During Method Evidence

Post-translational Modifications


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Site Modification Modifier Reference

Interaction Annotations


Genetic Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Assay Annotation Action Modification Source Reference

Functional Complementation Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Species Gene ID Strain background Direction Details Source Reference