ArticleNature chemistry2023
Biosynthesis and biotechnological production of the anti-obesity agent celastrol.
Article in Nature chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 48 citations in OpenAlex.
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- Gamma-selinene synthase catalyzes the first step of dihydroagarofuran sesquiterpene alkaloid biosynthesis in Tripterygium.Science China. Life sciences · 2025Article
- Characterization of global research trends and prospects on celastrol, a principal bioactive ingredient ofPharmaceutical biology · 2025Article
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- Modeling for understanding and engineering metabolism.QRB discovery · 2025Article
- Unveiling the Anti-Obesity Potential of Thunder God Vine: Network Pharmacology and Computational Insights into Celastrol-like Molecules.International journal of molecular sciences · 2024Article
- Intein-mediated temperature control for complete biosynthesis of sanguinarine and its halogenated derivatives in yeast.Nature communications · 2024Article
- Concentration Recognition-Based Auto-Dynamic Regulation System (CRUISE) Enabling Efficient Production of Higher Alcohols.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Strategies, Achievements, and Potential Challenges of Plant and Microbial Chassis in the Biosynthesis of Plant Secondary Metabolites.Molecules (Basel, Switzerland) · 2024Review
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11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity is a major health risk still lacking effective pharmacological treatment. A potent anti-obesity agent, celastrol, has been identified in the roots of Tripterygium wilfordii. However, an efficient synthetic method is required to better explore its biological utility. Here we elucidate the 11 missing steps for the celastrol biosynthetic route to enable its de novo biosynthesis in yeast. First, we reveal the cytochrome P450 enzymes that catalyse the four oxidation steps that produce the key intermediate celastrogenic acid. Subsequently, we show that non-enzymatic decarboxylation-triggered activation of celastrogenic acid leads to a cascade of tandem catechol oxidation-driven double-bond extension events that generate the characteristic quinone methide moiety of celastrol. Using this acquired knowledge, we have developed a method for producing celastrol starting from table sugar. This work highlights the effectiveness of combining plant biochemistry with metabolic engineering and chemistry for the scalable synthesis of complex specialized metabolites.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.