ArticleMicrobial cell factories2020
Integrating pathway elucidation with yeast engineering to produce polpunonic acid the precursor of the anti-obesity agent celastrol.
Article in Microbial cell factories, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 44 citations in OpenAlex.
- Metabolic engineering of Phaeodactylum tricornutum for heterologous production of the plant triterpenoid friedelin.Microbial cell factories · 2025Article
- Two-Phase Fermentation Systems for Microbial Production of Plant-Derived Terpenes.Molecules (Basel, Switzerland) · 2024Review
- Biosynthesis and biotechnological production of the anti-obesity agent celastrol.Nature chemistry · 2023Article
- Optogenetic control of beta-carotene bioproduction in yeast across multiple lab-scales.Frontiers in bioengineering and biotechnology · 2023Article
- Tuning heterologous glucan biosynthesis in yeast to understand and exploit plant starch diversity.BMC biology · 2022Article
- The tomato cytochrome P450 CYP712G1 catalyses the double oxidation of orobanchol en route to the rhizosphere signalling strigolactone, solanacol.The New phytologist · 2022Article
- Tripterygium wilfordii cytochrome P450s catalyze the methyl shift and epoxidations in the biosynthesis of triptonide.Nature communications · 2022Article
- Genome-wide analysis of MYB family genes inPlant direct · 2022Article
- Metabolic Engineering ofFrontiers in bioengineering and biotechnology · 2022Article
- Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants.Beilstein journal of organic chemistry · 2022Review
- The Therapeutic Potential of Celastrol in Central Nervous System Disorders: Highlights from In Vitro and In Vivo Approaches.Molecules (Basel, Switzerland) · 2021Review
- Fermentation Strategies for Production of Pharmaceutical Terpenoids in Engineered Yeast.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Engineered butyrate-producing bacteria prevents high fat diet-induced obesity in mice.Microbial cell factories · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundCelastrol is a promising anti-obesity agent that acts as a sensitizer of the protein hormone leptin. Despite its potent activity, a sustainable source of celastrol and celastrol derivatives for further pharmacological studies is lacking.
resultsTo elucidate the celastrol biosynthetic pathway and reconstruct it in Saccharomyces cerevisiae, we mined a root-transcriptome of Tripterygium wilfordii and identified four oxidosqualene cyclases and 49 cytochrome P450s as candidates to be involved in the early steps of celastrol biosynthesis. Using functional screening of the candidate genes in Nicotiana benthamiana, TwOSC4 was characterized as a novel oxidosqualene cyclase that produces friedelin, the presumed triterpenoid backbone of celastrol. In addition, three P450s (CYP712K1, CYP712K2, and CYP712K3) that act downstream of TwOSC4 were found to effectively oxidize friedelin and form the likely celastrol biosynthesis intermediates 29-hydroxy-friedelin and polpunonic acid. To facilitate production of friedelin, the yeast strain AM254 was constructed by deleting UBC7, which afforded a fivefold increase in friedelin titer. This platform was further expanded with CYP712K1 to produce polpunonic acid and a method for the facile extraction of products from the yeast culture medium, resulting in polpunonic acid titers of 1.4 mg/L.
conclusionOur study elucidates the early steps of celastrol biosynthesis and paves the way for future biotechnological production of this pharmacologically promising compound in engineered yeast strains.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.