ArticleProceedings of the National Academy of Sciences of the United States of America2022
Mechanistic analysis of carbon-carbon bond formation by deoxypodophyllotoxin synthase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 28 citations in OpenAlex.
- Uncovering the Origins of Selectivity in Non-Heme Iron Dioxygenase-Catalyzed Tropolone Biosynthesis.The journal of physical chemistry. B · 2025Article
- Discovery of Noncanonical Iron and 2-Oxoglutarate Dependent Enzymes Involved in C-C and C-N Bond Formation in Biosynthetic Pathways.ACS bio & med chem Au · 2025Review
- Comparison of a Nonheme Iron Cyclopropanase with a Homologous Hydroxylase Reveals Mechanistic Features Associated with Distinct Reaction Outcomes.Journal of the American Chemical Society · 2025Article
- Genomic characterization and identification of candidate genes for putative podophyllotoxin biosynthesis pathway in Penicillium herquei HGN12.1C.Microbial biotechnology · 2024Article
- Recent advances in enzymatic carbon-carbon bond formation.RSC advances · 2024Review
- The Unique Role of the Second Coordination Sphere to Unlock and Control Catalysis in Nonheme Fe(II)/2-Oxoglutarate Histone Demethylase KDM2A.Inorganic chemistry · 2024Article
- Oxidative modification of free-standing amino acids by Fe(II)/αKG-dependent oxygenases.Engineering microbiology · 2023Review
- Five decades of metalloenzymology.The Enzymes · 2023Review
- Taming the radical cation intermediate enabled one-step access to structurally diverse lignans.Nature communications · 2022Article
- Mechanism of Methyldehydrofosmidomycin Maturation: Use Olefination to Enable Chain Elongation.Journal of the American Chemical Society · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deoxypodophyllotoxin contains a core of four fused rings (A to D) with three consecutive chiral centers, the last being created by the attachment of a peripheral trimethoxyphenyl ring (E) to ring C. Previous studies have suggested that the iron(II)- and 2-oxoglutarate-dependent (Fe/2OG) oxygenase, deoxypodophyllotoxin synthase (DPS), catalyzes the oxidative coupling of ring B and ring E to form ring C and complete the tetracyclic core. Despite recent efforts to deploy DPS in the preparation of deoxypodophyllotoxin analogs, the mechanism underlying the regio- and stereoselectivity of this cyclization event has not been elucidated. Herein, we report 1) two structures of DPS in complex with 2OG and (±)-yatein, 2) in vitro analysis of enzymatic reactivity with substrate analogs, and 3) model reactions addressing DPS's catalytic mechanism. The results disfavor a prior proposal of on-pathway benzylic hydroxylation. Rather, the DPS-catalyzed cyclization likely proceeds by hydrogen atom abstraction from C7', oxidation of the benzylic radical to a carbocation, Friedel-Crafts-like ring closure, and rearomatization of ring B by C6 deprotonation. This mechanism adds to the known pathways for transformation of the carbon-centered radical in Fe/2OG enzymes and suggests what types of substrate modification are likely tolerable in DPS-catalyzed production of deoxypodophyllotoxin analogs.
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.