ArticleJournal of medicinal chemistry2020
Characterization of TnmH as an
Article in Journal of medicinal chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- DVD-IgG1 antibody-drug conjugates: Expanding the landscape of targeted cancer therapy.Current opinion in chemical biology · 2026Review
- Enediyne natural product biosynthesis unified by a diiodotetrayne intermediate.Nature chemical biology · 2024Article
- Biochemical and Structural Studies of the Carminomycin 4-Journal of natural products · 2024Article
- Structure of methyltransferase RedM that forms the dimethylpyrrolinium of the bisindole reductasporine.The Journal of biological chemistry · 2024Article
- Normal and Aberrant Methyltransferase Activities Give Insights into the Final Steps of Dynemicin A Biosynthesis.Journal of the American Chemical Society · 2023Article
- Application of a Biocatalytic Strategy for the Preparation of Tiancimycin-Based Antibody-Drug Conjugates Revealing Key Insights into Structure-Activity Relationships.Journal of medicinal chemistry · 2023Article
- Intramolecular C-C Bond Formation Links Anthraquinone and Enediyne Scaffolds in Tiancimycin Biosynthesis.Journal of the American Chemical Society · 2022Article
- Functionalized 10-Membered Aza- and Oxaenediynes through the Nicholas Reaction.Molecules (Basel, Switzerland) · 2022Article
- Deciphering the pathway-specific regulatory network for production of ten-membered enediyne Tiancimycins in Streptomyces sp. CB03234-S.Microbial cell factories · 2022Article
- Functional Characterization of Cytochrome P450 Hydroxylase YpmL in Yangpumicin A Biosynthesis and Its Application for Anthraquinone-Fused Enediyne Structural Diversification.Organic letters · 2022Article
- Cytochrome P450 Hydroxylase TnmL Catalyzing Sequential Hydroxylation with an Additional Proofreading Activity in Tiancimycin Biosynthesis.ACS chemical biology · 2021Article
- Submerged fermentation of Streptomyces uncialis providing a biotechnology platform for uncialamycin biosynthesis, engineering, and production.Journal of industrial microbiology & biotechnology · 2021Article
- Enzyme-mediated bioorthogonal technologies: catalysts, chemoselective reactions and recent methyltransferase applications.Current opinion in biotechnology · 2021Review
- Challenges and Opportunities to Develop Enediyne Natural Products as Payloads for Antibody-Drug Conjugates.Antibody therapeutics · 2021Article
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Authors and funding
11 authors.
Funding
Abstract
The enediynes are among the most cytotoxic molecules known, and their use as anticancer drugs has been successfully demonstrated by targeted delivery. Clinical advancement of the anthraquinone-fused enediynes has been hindered by their low titers and lack of functional groups to enable the preparation of antibody-drug conjugates (ADCs). Here we report biochemical and structural characterization of TnmH from the tiancimycin (TNM) biosynthetic pathway, revealing that (i) TnmH catalyzes regiospecific methylation at the C-7 hydroxyl group, (ii) TnmH exhibits broad substrate promiscuity toward hydroxyanthraquinones and S-alkylated SAM analogues and catalyzes efficient installation of reactive alkyl handles, (iii) the X-ray crystal structure of TnmH provides the molecular basis to account for its broad substrate promiscuity, and (iv) TnmH as a biocatalyst enables the development of novel conjugation strategies to prepare antibody-TNM conjugates. These findings should greatly facilitate the construction and evaluation of antibody-TNM conjugates as next-generation ADCs for targeted chemotherapy.
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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.