ArticleJournal of bacteriology1999
Genetic localization and molecular characterization of two key genes (mitAB) required for biosynthesis of the antitumor antibiotic mitomycin C.
Article in Journal of bacteriology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 31 citations in OpenAlex.
- Genomic and Metabolomic Insights into the Antimicrobial Activities and Plant-Promoting Potential ofMicroorganisms · 2025Article
- Modifications of Protein-Bound Substrates by Trans-Acting Enzymes in Natural Products Biosynthesis.Chembiochem : a European journal of chemical biology · 2024Review
- Modifications of Acyl Carrier Protein-Bound Glycosylated Polyketides in Pactamycin Biosynthesis.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Glycosylation of acyl carrier protein-bound polyketides during pactamycin biosynthesis.Nature chemical biology · 2019Article
- Mitomycinoid alkaloids: mechanism of action, biosynthesis, total syntheses, and synthetic approaches.Chemical reviews · 2013Review
- Natural products synthesis: enabling tools to penetrate Nature's secrets of biogenesis and biomechanism.The Journal of organic chemistry · 2011Review
- Molecular insights on the biosynthesis of antitumour compounds by actinomycetes.Microbial biotechnology · 2011Review
- Mitomycins syntheses: a recent update.Beilstein journal of organic chemistry · 2009Article
- Synthesis of potential early-stage intermediates in the biosynthesis of FR900482 and mitomycin C.Organic letters · 2009Article
- Species-specific secondary metabolite production in marine actinomycetes of the genus Salinispora.Applied and environmental microbiology · 2007Article
- Mitomycin resistance in Streptomyces lavendulae includes a novel drug-binding-protein-dependent export system.Journal of bacteriology · 1999Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mitomycin C (MC) is an antitumor antibiotic derived biosynthetically from 3-amino-5-hydroxybenzoic acid (AHBA), D-glucosamine, and carbamoyl phosphate. A gene (mitA) involved in synthesis of AHBA has been identified and found to be linked to the MC resistance locus, mrd, in Streptomyces lavendulae. Nucleotide sequence analysis showed that mitA encodes a 388-amino-acid protein that has 71% identity (80% similarity) with the rifamycin AHBA synthase from Amycolatopsis mediterranei, as well as with two additional AHBA synthases from related ansamycin antibiotic-producing microorganisms. Gene disruption and site-directed mutagenesis of the S. lavendulae chromosomal copy of mitA completely blocked the production of MC. The function of mitA was confirmed by complementation of an S. lavendulae strain containing a K191A mutation in MitA with AHBA. A second gene (mitB) encoding a 272-amino-acid protein (related to a group of glycosyltransferases) was identified immediately downstream of mitA that upon disruption resulted in abrogation of MC synthesis. This work has localized a cluster of key genes that mediate assembly of the unique mitosane class of natural products.
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