ArticleThe Journal of biological chemistry2010
Origin of the allyl group in FK506 biosynthesis.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 78 citations in OpenAlex.
- TridentSynth: a webtool for the retrosynthesis of molecules using chimeric type I polyketide synthases and chemoenzymatic pathways.Nucleic acids research · 2026Article
- Engineering of FK520 polyketide synthase for rapid access to quality control reference standards.Microbial cell factories · 2025Article
- Merging the computational design of chimeric type I polyketide synthases with enzymatic pathways for chemical biosynthesis.Nature communications · 2025Article
- Regulatory orchestration of FK506 biosynthesis iniScience · 2025Article
- Efficient and Selective Biosynthesis of a Precursor-Directed FK506 Analogue: Paving the Way for Click Chemistry.Journal of natural products · 2025Article
- Modifications of Protein-Bound Substrates by Trans-Acting Enzymes in Natural Products Biosynthesis.Chembiochem : a European journal of chemical biology · 2024Review
- Optimization of FK-506 production in Streptomyces tsukubaensis by modulation of Crp-mediated regulation.Applied microbiology and biotechnology · 2023Article
- Optimization of the precursor supply for an enhanced FK506 production inFrontiers in bioengineering and biotechnology · 2022Article
- Review
- Bioengineering of Anti-Inflammatory Natural Products.ChemMedChem · 2021Review
- Unraveling Nutritional Regulation of Tacrolimus Biosynthesis inAntibiotics (Basel, Switzerland) · 2018Review
- Substrate Specificity of Acyltransferase Domains for Efficient Transfer of Acyl Groups.Frontiers in microbiology · 2018Article
- dRNA-seq transcriptional profiling of the FK506 biosynthetic gene cluster in Streptomyces tsukubaensis NRRL18488 and general analysis of the transcriptome.RNA biology · 2017Article
- Combining metabolomics and network analysis to improve tacrolimus production in Streptomyces tsukubaensis using different exogenous feedings.Journal of industrial microbiology & biotechnology · 2017Article
- Draft Genome Sequence of the Tacrolimus-Producing BacteriumGenome announcements · 2017Article
- FkbN and Tcs7 are pathway-specific regulators of the FK506 biosynthetic gene cluster in Streptomyces tsukubaensis L19.Journal of industrial microbiology & biotechnology · 2016Article
- Characterization of Discrete Phosphopantetheinyl Transferases in Streptomyces tsukubaensis L19 Unveils a Complicate Phosphopantetheinylation Network.Scientific reports · 2016Article
- The biosynthetic pathway of FK506 and its engineering: from past achievements to future prospects.Journal of industrial microbiology & biotechnology · 2016Review
- Heterologous Production of the Marine Myxobacterial Antibiotic Haliangicin and Its Unnatural Analogues Generated by Engineering of the Biochemical Pathway.Scientific reports · 2016Article
- Roles of the crotonyl-CoA carboxylase/reductase homologues in acetate assimilation and biosynthesis of immunosuppressant FK506 in Streptomyces tsukubaensis.Microbial cell factories · 2015Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FK506 (tacrolimus) is a secondary metabolite with a potent immunosuppressive activity, currently registered for use as immunosuppressant after organ transplantation. FK506 and FK520 are biogenetically related natural products that are synthesized by combined polyketide synthase/nonribosomal peptide synthetase systems. The entire gene cluster for biosynthesis of FK520 from Streptomyces hygroscopicus var. ascomyceticus has been cloned and sequenced. On the other hand, the FK506 gene cluster from Streptomyces sp. MA6548 (ATCC55098) was sequenced only partially, and it was reasonable to expect that additional genes would be required for the provision of substrate supply. Here we report the identification of a previously unknown region of the FK506 gene cluster from Streptomyces tsukubaensis NRRL 18488 containing genes encoding the provision of unusual building blocks for FK506 biosynthesis as well as a regulatory gene. Among others, we identified a group of genes encoding biosynthesis of the extender unit that forms the allyl group at carbon 21 of FK506. Interestingly, we have identified a small independent diketide synthase system involved in the biosynthesis of the allyl group. Inactivation of one of these genes, encoding an unusual ketosynthase domain, resulted in an FK506 nonproducing strain, and the production was restored when a synthetic analog of the allylmalonyl-CoA extender unit was added to the cultivation medium. Based on our results, we propose a biosynthetic pathway for the provision of an unusual five-carbon extender unit, which is carried out by a novel diketide synthase complex.
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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.