ArticleScientific reports2018
Filling the Gaps in the Kirromycin Biosynthesis: Deciphering the Role of Genes Involved in Ethylmalonyl-CoA Supply and Tailoring Reactions.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 22 citations in OpenAlex.
- Actinoplanes kirromycinicus sp. nov., isolated from soil.The Journal of antibiotics · 2024Article
- Discovery of Streptomyces species CS-62, a novel producer of the Acinetobacter baumannii selective antibiotic factumycin.Journal of industrial microbiology & biotechnology · 2024Article
- Biosynthesis of Aurodox, a Type III Secretion System Inhibitor from Streptomyces goldiniensis.Applied and environmental microbiology · 2022Article
- Engineering ofMolecules (Basel, Switzerland) · 2021Article
- Structural Basis for Enzymatic Off-Loading of Hybrid Polyketides by Dieckmann Condensation.ACS chemical biology · 2020Article
- An Update on Molecular Tools for Genetic Engineering of Actinomycetes-The Source of Important Antibiotics and Other Valuable Compounds.Antibiotics (Basel, Switzerland) · 2020Review
- Comparative Transcriptomic Analysis Uncovers Genes Responsible for the DHA Enhancement in the MutantMicroorganisms · 2020Article
- Highly efficient DSB-free base editing for streptomycetes with CRISPR-BEST.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Comparison of Antibiotic Resistance Mechanisms in Antibiotic-Producing and Pathogenic Bacteria.Molecules (Basel, Switzerland) · 2019Review
- Acyltransferases as Tools for Polyketide Synthase Engineering.Antibiotics (Basel, Switzerland) · 2018Review
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kirromycin is the main product of the soil-dwelling Streptomyces collinus Tü 365. The elucidation of the biosynthetic pathway revealed that the antibiotic is synthesised via a unique combination of trans-/cis-AT type I polyketide synthases and non-ribosomal peptide synthetases (PKS I/NRPS). This was the first example of an assembly line integrating the three biosynthetic principles in one pathway. However, information about other enzymes involved in kirromycin biosynthesis remained scarce. In this study, genes encoding tailoring enzymes KirM, KirHVI, KirOI, and KirOII, and the putative crotonyl-CoA reductase/carboxylase KirN were deleted, complemented, and the emerged products analysed by HPLC-HRMS and MS/MS. Derivatives were identified in mutants ΔkirM, ΔkirHVI, ΔkirOI, and ΔkirOII. The products of ΔkirOI, ΔkirOII, and kirHVI were subjected to 2D-NMR for structure elucidation. Our results enabled functional assignment of those enzymes, demonstrating their involvement in kirromycin tailoring. In the ΔkirN mutant, the production of kirromycin was significantly decreased. The obtained data enabled us to clarify the putative roles of the studied enzymes, ultimately allowing us to fill many of the missing gaps in the biosynthesis of the complex antibiotic. Furthermore, this collection of mutants can serve as a toolbox for generation of new kirromycins.
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