ArticleApplied and environmental microbiology2006
Isolation, characterization, and heterologous expression of the biosynthesis gene cluster for the antitumor anthracycline steffimycin.
Article in Applied and environmental microbiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 109 citations in OpenAlex.
- Harnessing Actinobacteria secondary metabolites for tuberculosis drug discovery: Historical trends, current status and future outlooks.Natural products and bioprospecting · 2025Review
- Metagenomics approaches in the discovery and development of new bioactive compound of 8-demethoxy-10-deoxysteffimycin from mangrove sediments.3 Biotech · 2024Article
- Diverse Combinatorial Biosynthesis Strategies for C-H Functionalization of Anthracyclinones.ACS synthetic biology · 2024Article
- Complete sequences of pIJ101-based Streptomyces-Escherichia coli shuttle vectors.Access microbiology · 2024Article
- ActVI-ORFA directs metabolic flux towards actinorhodin by preventing intermediate degradation.PloS one · 2024Article
- Metabolic engineering ofEngineering microbiology · 2022Review
- Bioinformatic comparison of three Embleya species and description of steffimycins production by Embleya sp. NF3.Applied microbiology and biotechnology · 2022Article
- Review
- Biosynthesis of the Tricyclic Aromatic Type II Polyketide Rishirilide: New Potential Third Ring Oxygenation after Three Cyclization Steps.Molecular biotechnology · 2021Article
- Cas12a-assisted precise targeted cloning using in vivo Cre-lox recombination.Nature communications · 2021Article
- Review
- Steffimycin E, a new anti-mycobacterial agent against Mycobacterium avium complex, produced by Streptomyces sp. OPMA02852.The Journal of antibiotics · 2020Article
- Heterologous reconstitution of the biosynthesis pathway for 4-demethyl-premithramycinone, the aglycon of antitumor polyketide mithramycin.Microbial cell factories · 2020Article
- Comparative Genomic Insights into Secondary Metabolism Biosynthetic Gene Cluster Distributions of MarineMarine drugs · 2019Article
- Antimycobacterial activity of an anthracycline produced by an endophyte isolated from Amphipterygium adstringens.Molecular biology reports · 2018Article
- Lysoquinone-TH1, a New Polyphenolic Tridecaketide Produced by Expressing the Lysolipin Minimal PKS II inAntibiotics (Basel, Switzerland) · 2018Article
- Self-resistance guided genome mining uncovers new topoisomerase inhibitors from myxobacteria.Chemical science · 2018Article
- High-Yield Production of Herbicidal Thaxtomins and Thaxtomin Analogs in a Nonpathogenic Streptomyces Strain.Applied and environmental microbiology · 2018Article
- Searching for Glycosylated Natural Products in Actinomycetes and Identification of Novel Macrolactams and Angucyclines.Frontiers in microbiology · 2018Article
- One-Pot Enzymatic Total Synthesis of Presteffimycinone, an Early Intermediate of the Anthracycline Antibiotic Steffimycin Biosynthesis.Organic letters · 2017Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The biosynthetic gene cluster for the aromatic polyketide steffimycin of the anthracycline family has been cloned and characterized from "Streptomyces steffisburgensis" NRRL 3193. Sequence analysis of a 42.8-kbp DNA region revealed the presence of 36 open reading frames (ORFs) (one of them incomplete), 24 of which, spanning 26.5 kb, are probably involved in steffimycin biosynthesis. They code for all the activities required for polyketide biosynthesis, tailoring, regulation, and resistance but show no evidence of genes involved in L-rhamnose biosynthesis. The involvement of the cluster in steffimycin biosynthesis was confirmed by expression of a region of about 15 kb containing 15 ORFS, 11 of them forming part of the cluster, in the heterologous host Streptomyces albus, allowing the isolation of a biosynthetic intermediate. In addition, the expression in S. albus of the entire cluster, contained in a region of 34.8 kb, combined with the expression of plasmid pRHAM, directing the biosynthesis of L-rhamnose, led to the production of steffimycin. Inactivation of the stfX gene, coding for a putative cyclase, revealed that this enzymatic activity participates in the cyclization of the fourth ring, making the final steps in the biosynthesis of the steffimycin aglycon similar to those in the biosynthesis of jadomycin or rabelomycin. Inactivation of the stfG gene, coding for a putative glycosyltransferase involved in the attachment of L-rhamnose, allowed the production of a new compound corresponding to the steffimycin aglycon compound also observed in S. albus upon expression of the entire cluster.
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