ArticleBiochemistry2013
Structure and stereospecificity of the dehydratase domain from the terminal module of the rifamycin polyketide synthase.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- C-terminal dimerization motifs control asynchronous chain elongation during modular polyketide biosynthesis.The Journal of biological chemistry · 2026Article
- Elucidation of interface interactions between a dehydratase domain and an acyl carrier protein in cremimycin polyketide synthase.FEBS letters · 2025Article
- Structure and Mechanisms of Assembly-Line Polyketide Synthases.Annual review of biochemistry · 2024Review
- Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain.Beilstein journal of organic chemistry · 2024Article
- Structure of a modular polyketide synthase reducing region.Structure (London, England : 1993) · 2023Article
- C-N bond formation by a polyketide synthase.Nature communications · 2023Article
- Conservation of griseofulvin genes in the gsf gene cluster among fungal genomes.G3 (Bethesda, Md.) · 2022Article
- Biosynthesis of 6-Hydroxymellein Requires a Collaborating Polyketide Synthase-like Enzyme.Angewandte Chemie (International ed. in English) · 2021Article
- Site directed mutagenesis as a precision tool to enable synthetic biology with engineered modular polyketide synthases.Synthetic and systems biotechnology · 2020Review
- Diversification of polyketide structuresMedChemComm · 2019Review
- Structural insights into dehydratase substrate selection for the borrelidin and fluvirucin polyketide synthases.Journal of industrial microbiology & biotechnology · 2019Article
- Thioesterase-Catalyzed Aminoacylation and Thiolation of Polyketides in Fungi.Journal of the American Chemical Society · 2019Article
- Structural Basis of Polyketide Synthase O-Methylation.ACS chemical biology · 2018Article
- pH-Rate profiles establish that polyketide synthase dehydratase domains utilize a single-base mechanism.Organic & biomolecular chemistry · 2018Article
- The architectures of iterative type I PKS and FAS.Natural product reports · 2018Review
- Protein-protein interactions in "cis-AT" polyketide synthases.Natural product reports · 2018Review
- Molecular Basis for Olefin Rearrangement in the Gephyronic Acid Polyketide Synthase.ACS chemical biology · 2018Article
- Stereospecific Formation of Z-Trisubstituted Double Bonds by the Successive Action of Ketoreductase and Dehydratase Domains from trans-AT Polyketide Synthases.Biochemistry · 2018Article
- Stereospecific Formation of E- and Z-Disubstituted Double Bonds by Dehydratase Domains from Modules 1 and 2 of the Fostriecin Polyketide Synthase.Journal of the American Chemical Society · 2017Article
- Engineered polyketides: Synergy between protein and host level engineering.Synthetic and systems biotechnology · 2017Review
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4 authors at 2 institutions in 1 country.
Funding
Abstract
RifDH10, the dehydratase domain from the terminal module of the rifamycin polyketide synthase, catalyzes the stereospecific syn dehydration of the model substrate (2S,3S)-2-methyl-3-hydroxypentanoyl-RifACP10, resulting in the exclusive formation of (E)-2-methyl-2-pentenoyl-RifACP10. RifDH10 does not dehydrate any of the other three diastereomeric, RifACP10-bound, diketide thioester substrates. On the other hand, when EryACP6, from the sixth module of the erythromycin polyketide synthase, is substituted for RifACP10, RifDH10 stereospecifically dehydrates only (2R,3R)-2-methyl-3-hydroxypentanoyl-EryACP6 to give exclusively (E)-2-methyl-2-pentenoyl-EryACP6, with no detectable dehydration of any of the other three diastereomeric, EryACP6-bound, diketides. An identical alteration in substrate diastereospecificity was observed for the corresponding N-acetylcysteamine or pantetheine thioester analogues, regardless of acyl chain length or substitution pattern. Incubation of (2RS)-2-methyl-3-ketopentanoyl-RifACP10 with the didomain reductase-dehydratase RifKR10-RifDH10 yielded (E)-2-methyl-2-pentenoyl-RifACP10, the expected product of syn dehydration of (2S,3S)-2-methyl-3-hydroxypentanoyl-RifACP10, while incubation with the corresponding EryACP6-bound substrate, (2RS)-2-methyl-3-ketopentanoyl-EryACP6, gave only the reduction product (2S,3S)-2-methyl-3-hydroxypentanoyl-EryACP6 with no detectable dehydration. These results establish the intrinsic syn dehydration stereochemistry and substrate diastereoselectivity of RifDH10 and highlight the critical role of the natural RifACP10 domain in chaperoning the proper recognition and processing of the natural ACP-bound undecaketide substrate. The 1.82 Å resolution structure of RifDH10 reveals the atomic-resolution details of the active site and allows modeling of the syn dehydration of the (2S,3S)-2-methyl-3-hydroxyacyl-RifACP10 substrate. These results suggest that generation of the characteristic cis double bond of the rifamycins occurs after formation of the full-length RifACP10-bound acyclic trans-unsaturated undecaketide intermediate, most likely during the subsequent macrolactamization catalyzed by the amide synthase RifF.
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