ArticleProceedings of the National Academy of Sciences of the United States of America2012
Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis that pooled it.
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Who cites it
133 citing papers in PubMed, 1 synthesis or guideline pooled it, 293 citations in OpenAlex.
- Post-Harvest Operations to Generate High-Quality Medicinal Cannabis Products: A Systemic Review.Molecules (Basel, Switzerland) · 2022Pooled it
- Epigenome Editing for Cannabinoid Yield: Targets, Tools, and Priorities inInternational journal of molecular sciences · 2026Review
- Ancient origins of alkaloid biosynthesis in medicinal clubmosses.bioRxiv : the preprint server for biology · 2026Article
- Resurrected Ancestral Cannabis Enzymes Unveil the Origin and Functional Evolution of Cannabinoid Synthases.Plant biotechnology journal · 2026Article
- De novo synthesis of plant polyketide plumbagin in yeast: a platform for sustainable production of naphthoquinones.Natural products and bioprospecting · 2026Article
- Insights into glandular trichome biology from analysis of organ-specific gene expression programmes in cannabis, hop and tomato.The Plant journal : for cell and molecular biology · 2026Article
- Cannabis: from crop to shop-some insights about stability to access quality control.Journal of cannabis research · 2026Review
- Therapeutic potential of acidic cannabinoids: an update.Journal of cannabis research · 2026Review
- Combination of red and UV-A light enhances hemp (Cannabis sativa L.) inflorescence yield and cannabinoid content.Scientific reports · 2025Article
- Glycosylated cannabinoids inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Assessing the adaptive role of cannabidivarinic acid (CBDVA) in aphid defense in Cannabis sativa.Journal of cannabis research · 2025Article
- Discovery of major QTL and a massive haplotype associated with cannabinoid biosynthesis in drug-type Cannabis.The plant genome · 2025Article
- Article
- Impact of heterologous expression of Cannabis sativa tetraketide synthase on Phaeodactylum tricornutum metabolic profile.Biotechnology for biofuels and bioproducts · 2025Article
- An In Vitro Phytohormone Survey Reveals Concerted Regulation of the Cannabis Glandular Trichome Disc Cell Proteome.Plants (Basel, Switzerland) · 2025Article
- Characterisation of Cannabis glandular trichome development reveals distinct features of cannabinoid biosynthesis.Plant cell reports · 2025Article
- Understanding the role of oxylipins inFrontiers in plant science · 2025Review
- Identification and Optimization of more Efficient Olivetolic Acid Synthases.Cannabis and cannabinoid research · 2024Article
- Genome-wide identification of cannabinoid biosynthesis genes in non-drug type Cannabis (Cannabis sativa L.) cultivar.Journal of cannabis research · 2024Article
- Effect of Hemp Extraction Procedures on Cannabinoid and Terpenoid Composition.Plants (Basel, Switzerland) · 2024Article
73 more citing papers are in PubMed but not listed here.
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6 authors at 2 institutions in 1 country.
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Abstract
Δ(9)-Tetrahydrocannabinol (THC) and other cannabinoids are responsible for the psychoactive and medicinal properties of Cannabis sativa L. (marijuana). The first intermediate in the cannabinoid biosynthetic pathway is proposed to be olivetolic acid (OA), an alkylresorcinolic acid that forms the polyketide nucleus of the cannabinoids. OA has been postulated to be synthesized by a type III polyketide synthase (PKS) enzyme, but so far type III PKSs from cannabis have been shown to produce catalytic byproducts instead of OA. We analyzed the transcriptome of glandular trichomes from female cannabis flowers, which are the primary site of cannabinoid biosynthesis, and searched for polyketide cyclase-like enzymes that could assist in OA cyclization. Here, we show that a type III PKS (tetraketide synthase) from cannabis trichomes requires the presence of a polyketide cyclase enzyme, olivetolic acid cyclase (OAC), which catalyzes a C2-C7 intramolecular aldol condensation with carboxylate retention to form OA. OAC is a dimeric α+β barrel (DABB) protein that is structurally similar to polyketide cyclases from Streptomyces species. OAC transcript is present at high levels in glandular trichomes, an expression profile that parallels other cannabinoid pathway enzymes. Our identification of OAC both clarifies the cannabinoid pathway and demonstrates unexpected evolutionary parallels between polyketide biosynthesis in plants and bacteria. In addition, the widespread occurrence of DABB proteins in plants suggests that polyketide cyclases may play an overlooked role in generating plant chemical diversity.
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