ArticleJournal of natural products2008
Mithramycin analogues generated by combinatorial biosynthesis show improved bioactivity.
Article in Journal of natural products, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 55 citations in OpenAlex.
- Digitoxose as powerful glycosyls for building multifarious glycoconjugates of natural products and un-natural products.Synthetic and systems biotechnology · 2024Review
- Metathramycin, a new bioactive aureolic acid discovered by heterologous expression of a metagenome derived biosynthetic pathway.RSC chemical biology · 2021Article
- Heterologous reconstitution of the biosynthesis pathway for 4-demethyl-premithramycinone, the aglycon of antitumor polyketide mithramycin.Microbial cell factories · 2020Article
- An "olivomycin A" derivative from a sponge-associated3 Biotech · 2019Article
- Novel bioactive natural products from bacteria via bioprospecting, genome mining and metabolic engineering.Microbial biotechnology · 2019Review
- The Mithralog EC-7072 Induces Chronic Lymphocytic Leukemia Cell Death by Targeting Tonic B-Cell Receptor Signaling.Frontiers in immunology · 2019Article
- Purification and characterization of a novel phloretin-2'-O-glycosyltransferase favoring phloridzin biosynthesis.Scientific reports · 2016Article
- Molecular insight into substrate recognition and catalysis of Baeyer-Villiger monooxygenase MtmOIV, the key frame-modifying enzyme in the biosynthesis of anticancer agent mithramycin.ACS chemical biology · 2013Article
- An efficient and cost-effective preparation of di-Tetrahedron letters · 2013Article
- Cooperation of two bifunctional enzymes in the biosynthesis and attachment of deoxysugars of the antitumor antibiotic mithramycin.Angewandte Chemie (International ed. in English) · 2012Article
- A novel mithramycin analogue with high antitumor activity and less toxicity generated by combinatorial biosynthesis.Journal of medicinal chemistry · 2012Article
- Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia.International journal of nanomedicine · 2012Article
- The crystal structure and mechanism of an unusual oxidoreductase, GilR, involved in gilvocarcin V biosynthesis.The Journal of biological chemistry · 2011Article
- The chromomycin CmmA acetyltransferase: a membrane-bound enzyme as a tool for increasing structural diversity of the antitumour mithramycin.Microbial biotechnology · 2011Article
- Molecular insights on the biosynthesis of antitumour compounds by actinomycetes.Microbial biotechnology · 2011Review
- Engineered biosynthesis of gilvocarcin analogues with altered deoxyhexopyranose moieties.Applied and environmental microbiology · 2011Article
- Crystal structure of Baeyer-Villiger monooxygenase MtmOIV, the key enzyme of the mithramycin biosynthetic pathway .Biochemistry · 2009Article
- Studies on the synthesis of durhamycin A: stereoselective synthesis of a model aglycone.Organic letters · 2008Article
- Generation of new derivatives of the antitumor antibiotic mithramycin by altering the glycosylation pattern through combinatorial biosynthesis.Chembiochem : a European journal of chemical biology · 2008Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Plasmid pLNBIV was used to overexpress the biosynthetic pathway of nucleoside-diphosphate (NDP)-activated l-digitoxose in the mithramycin producer Streptomyces argillaceus. This led to a "flooding" of the biosynthetic pathway of the antitumor drug mithramycin (MTM) with NDP-activated deoxysugars, which do not normally occur in the pathway, and consequently to the production of the four new mithramycin derivatives 1- 4 with altered saccharide patterns. Their structures reflect that NDP sugars produced by pLNBIV, namely, l-digitoxose and its biosynthetic intermediates, influenced the glycosyl transfer to positions B, D, and E, while positions A and C remained unaffected. All four new structures have unique, previously not found sugar decoration patterns, which arise from either overcoming the substrate specificity or inhibition of certain glycosyltransferases (GTs) of the MTM pathway with the foreign NDP sugars expressed by pLNBIV. An apoptosis TUNEL (=terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay revealed that compounds 1 (demycarosyl-3D-beta- d-digitoxosyl-MTM) and 3 (deoliosyl-3C-beta- d-mycarosyl-MTM) show improved activity (64.8 +/- 2% and 50.3 +/- 2.5% induction of apoptosis, respectively) against the estrogen receptor (ER)-positive human breast cancer cell line MCF-7 compared with the parent drug MTM (37.8 +/- 2.5% induction of apoptosis). In addition, compounds 1 and 4 (3A-deolivosyl-MTM) show significant effects on the ER-negative human breast cancer cell line MDA-231 (63.6 +/- 2% and 12.6 +/- 2.5% induction of apoptosis, respectively), which is not inhibited by the parent drug MTM itself (2.6 +/- 1.5% induction of apoptosis), but for which chemotherapeutic agents are urgently needed.
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