ArticleNature communications2022
Catalytic innovation underlies independent recruitment of polyketide synthases in cocaine and hyoscyamine biosynthesis.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 18 citations in OpenAlex.
- A Comprehensive Review on the Biosynthesis of Tropane Alkaloids.Molecules (Basel, Switzerland) · 2026Review
- A case study of evolutionary variability and determinism among type III polyketide synthases.Nature communications · 2026Article
- Convergence and parallelism in the evolution of plant metabolism.Journal of integrative plant biology · 2026Review
- Averrhoa carambola Leaf Extract Induces Apoptosis-Like Death with Increased ROS Generation in Leishmania donovani.Acta parasitologica · 2024Article
- Discovering a mitochondrion-localized BAHD acyltransferase involved in calystegine biosynthesis and engineering the production of 3β-tigloyloxytropane.Nature communications · 2024Article
- Multiple independent losses of the biosynthetic pathway for two tropane alkaloids in the Solanaceae family.Nature communications · 2023Article
- Emerging functions within the enzyme families of plant alkaloid biosynthesis.Phytochemistry reviews : proceedings of the Phytochemical Society of Europe · 2023Article
- Genomic and structural basis for evolution of tropane alkaloid biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Understanding how plants produce cocaine.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Geographically associated endophytic fungi contribute to the tropane alkaloids accumulation ofFrontiers in plant science · 2023Article
- Elucidation of tropane alkaloid biosynthesis inProceedings of the National Academy of Sciences of the United States of America · 2022Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tropane alkaloids such as hyoscyamine and cocaine are of importance in medicinal uses. Only recently has the hyoscyamine biosynthetic machinery become complete. However, the cocaine biosynthesis pathway remains only partially elucidated. Here we characterize polyketide synthases required for generating 3-oxo-glutaric acid from malonyl-CoA in cocaine biosynthetic route. Structural analysis shows that these two polyketide synthases adopt distinctly different active site architecture to catalyze the same reaction as pyrrolidine ketide synthase in hyoscyamine biosynthesis, revealing an unusual parallel/convergent evolution of biochemical function in homologous enzymes. Further phylogenetic analysis suggests lineage-specific acquisition of polyketide synthases required for tropane alkaloid biosynthesis in Erythroxylaceae and Solanaceae species, respectively. Overall, our work elucidates not only a key unknown step in cocaine biosynthesis pathway but also, more importantly, structural and biochemical basis for independent recruitment of polyketide synthases in tropane alkaloid biosynthesis, thus broadening the understanding of conservation and innovation of biosynthetic catalysts.
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