ArticleChemistry & biology2012
An unusual role for a mobile flavin in StaC-like indolocarbazole biosynthetic enzymes.
Article in Chemistry & biology, 2012. 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, 33 citations in OpenAlex.
- Decarboxylation in Natural Products Biosynthesis.JACS Au · 2024Review
- A multifunctional flavoprotein monooxygenase HspB for hydroxylation and C-C cleavage of 6-hydroxy-3-succinoyl-pyridine.Applied and environmental microbiology · 2024Article
- Ligand bound structure of a 6-hydroxynicotinic acid 3-monooxygenase provides mechanistic insights.Archives of biochemistry and biophysics · 2024Article
- Tetracycline-Inactivating Enzymes.Frontiers in microbiology · 2018Review
- Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function.Natural product reports · 2017Review
- Insights into Complex Oxidation during BE-7585A Biosynthesis: Structural Determination and Analysis of the Polyketide Monooxygenase BexE.ACS chemical biology · 2016Article
- One-carbon chemistry of oxalate oxidoreductase captured by X-ray crystallography.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Cytotoxic Indolocarbazoles from Actinomadura melliaura ATCC 39691.Journal of natural products · 2015Article
- Expansion of bisindole biosynthetic pathways by combinatorial construction.ACS synthetic biology · 2015Article
- Targeted metagenomics: finding rare tryptophan dimer natural products in the environment.Journal of the American Chemical Society · 2015Article
- Structures of the Apo and FAD-bound forms of 2-hydroxybiphenyl 3-monooxygenase (HbpA) locate activity hotspots identified by using directed evolution.Chembiochem : a European journal of chemical biology · 2015Article
- Crystallographic evidence of drastic conformational changes in the active site of a flavin-dependent N-hydroxylase.Biochemistry · 2014Article
- Characterization of an environmental DNA-derived gene cluster that encodes the bisindolylmaleimide methylarcyriarubin.Chembiochem : a European journal of chemical biology · 2014Article
- Discovery and synthetic refactoring of tryptophan dimer gene clusters from the environment.Journal of the American Chemical Society · 2013Article
- Cloning, characterization and heterologous expression of the indolocarbazole biosynthetic gene cluster from marine-derived Streptomyces sanyensis FMA.Marine drugs · 2013Article
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7 authors at 4 institutions in 1 country.
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Abstract
The indolocarbazole biosynthetic enzymes StaC, InkE, RebC, and AtmC mediate the degree of oxidation of chromopyrrolic acid on route to the natural products staurosporine, K252a, rebeccamycin, and AT2433-A1, respectively. Here, we show that StaC and InkE, which mediate a net 4-electron oxidation, bind FAD with a micromolar K(d), whereas RebC and AtmC, which mediate a net 8-electron oxidation, bind FAD with a nanomolar K(d) while displaying the same FAD redox properties. We further create RebC-10x, a RebC protein with ten StaC-like amino acid substitutions outside of previously characterized FAD-binding motifs and the complementary StaC-10x. We find that these mutations mediate both FAD affinity and product specificity, with RebC-10x displaying higher StaC activity than StaC itself. X-ray structures of this StaC catalyst identify the substrate of StaC as 7-carboxy-K252c and suggest a unique mechanism for this FAD-dependent enzyme.
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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.