Decoding the Biosynthetic Pathway of the Alkaloid Morphine with Bioinformatics

Document Type : Original Article

Authors

1 Agricultural Biotechnology Department, Faculty of Agriculture, Azarbaijan Shahid Madani University, Tabriz, Iran

2 Department of Animal Sciences, University of Tabriz, Tabriz, Iran

10.22126/atic.2025.11523.1182

Abstract

In 1803, the opium poppy was the source of Morphine, the first alkaloid extracted. Due to its diverse use and therapeutic applications, it is considered the most notable alkaloid and accounts for 42 out of all alkaloid substances. This study aimed to use bioinformatics techniques to investigate the biosynthesis pathway of morphine. It included the compilation of nine genes associated with this pathway, based on a thorough literature review. The genes were later confirmed with the NCBI BLAST tool. For examining gene interactions, the research used STRING, and Cytoscape was utilized to visualize the molecular interaction network. Additionally, CytoHubba was applied to pinpoint hub proteins in this network. The hub genes were examined for enrichment with the Kyoto Encyclopedia of Genes and Genomes (KEGG) using STRING, while Gene Ontology (GO) analysis was conducted through gprofiler. Furthermore, the promoter regions of important genes were analyzed using MEME. The metabolic processes involved in morphine production highlight that the gene network associated with the morphine pathway has wider functions beyond merely generating primary metabolites. An examination of the KEGG pathway highlighted the importance of metabolic pathways and the production of secondary metabolites. Additionally, a review of the promoter suggested that signal transduction might be involved in morphine synthesis. The main genes involved in the production of morphine are linked to several key plant pathways, given that morphine is categorized as a secondary metabolite. This study employs various bioinformatics tools to pinpoint and evaluate gene interactions and metabolic pathways, providing a better understanding of how morphine alkaloids are synthesized. This approach could help develop new methods for producing and extracting morphine, as well as improve agricultural practices related to medicinal plants.

Graphical Abstract

Decoding the Biosynthetic Pathway of the Alkaloid Morphine with Bioinformatics

Highlights

  • Information on the number and names of qualities included within the morphine biosynthetic pathway in somniferum was collected. Nine qualities related to morphine biosynthesis were obtained and NCBI was impacted to get protein arrangements
  • Nine groupings related to morphine biosynthesis proteins were entered into STRING program (form 10) (https: //stringdb.org) to anticipate their utilitarian intelligence with other proteins in P. somniferum
  • The 1 kb regions located upstream of the hub gene were obtained from the Ensembl plant web service (https://plants.ensembl.org). Conserved motifs within the sequences were detected using MEME Suite version 5.4.1 (meme.nbcr.net/meme/intro.html) with the default settings, but the P and E thresholds were adjusted to <0.01.
  • The purpose of this research was to uncover new genes and networks linked to the morphine biosynthetic pathway in somniferum, as well as to improve the comprehension of the relationship between biosynthetic genes and functional pathways. The STRING database generated 121 nodes and 672 edges (Fig. 1) from the overall interactions.
  • Upon inputting the names of the hub genes into the KEGG mapper color tool, we obtained Fig. 5. It is evident that there are two pathways (the primary pathway and the secondary pathway) for morphine synthesis. In the primary pathway, the alkaloid morphine is produced directly, while in the secondary pathway, codeine is synthesized first before morphine is generated.
  • Given the signaling function of hub genes, it is probable that these genes are positioned upstream of those involved in the production of morphine. The proteins they code for become activated when exposed to a variety of internal and external stimuli faced by the plant, including both biotic and abiotic stresses, which initiate a series of downstream signaling cascades.

Keywords

Main Subjects

References

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Available Online from 27 May 2025

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