First Total Synthesis of (±)‐Rabelomycin

Krohn, Karsten; Khanbabaee, Karamali

doi:10.1002/anie.199400991

Cited by 60 publications

(22 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All of the four acquired M12-metabolites (5-8) as well as another related compound, rabelomycin (9), 24 were fed to an early block mutant of the landomycin biosynthesis to check whether they were intermediates of landomycin E biosynthesis. Rabelomycin (9) was isolated from the mutant S. fradiae ΔM.…”

Section: Feeding Experimentsmentioning

confidence: 99%

Identification of the Function of Gene lndM2 Encoding a Bifunctional Oxygenase-Reductase Involved in the Biosynthesis of the Antitumor Antibiotic Landomycin E by Streptomyces globisporus 1912 Supports the Originally Assigned Structure for Landomycinone

et al. 2004

View full text Add to dashboard Cite

The angucycline antibiotic family of the landomycins displays potent antitumor activity. To elucidate early post polyketide synthase (PKS) tailoring steps of the landomycin E biosynthetic pathway in Streptomyces globisporus 1912, the mutant S. globisporus M12 was prepared through gene replacement experiment of lndM2. It encodes an enzyme with putative oxygenase and reductase domains, according to sequencing of the gene and its counterpart lanM2 from S. cyanogenus S136 landomycin A biosynthetic gene cluster. The isolation of the novel shunt products 11-hydroxytetrangomycin and 4-hydroxytetrangomycin along with the well-known angucyclines tetrangomycin and tetrangulol from the culture of S. globisporus M12 provides evidence for the © 2005 American Chemical Society jrohr2@uky.edu. Supporting Information Available: Original NMR spectra obtained after the acetate feeding experiments on landomycin A and a newly generated 1 H NMR spectrum of natural landomycinone supporting the original landomycin structure. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript involvement of lndM2 in the early biosynthetic pathway of the landomycins, in particular in the formation of the alicyclic 6-hydroxy function of the landomycin aglycon. We therefore propose LndM2 to be responsible for both hydroxylation of the 6-position and its subsequent reduction. These reactions are necessary before the glycosylation reactions can occur. The results are in agreement with the originally published structure of landomycin but do not support the recently suggested revised structure.

show abstract

Section: Feeding Experimentsmentioning

confidence: 99%

Identification of the Function of Gene lndM2 Encoding a Bifunctional Oxygenase-Reductase Involved in the Biosynthesis of the Antitumor Antibiotic Landomycin E by Streptomyces globisporus 1912 Supports the Originally Assigned Structure for Landomycinone

et al. 2004

View full text Add to dashboard Cite

show abstract

“…During our search for further new cytotoxic landomycin analogues, a fermentation of Streptomyces cyanogenus K62 in SG-medium was carried out which afforded four new angucyclin(on)es: 11-deoxylandomycinone ( 1 ), and landomycins X–Z ( 2 – 4 ) along with the known compounds tetrangulol ( 11 ), tetrangomycin ( 12 ), landomycins M ( 8 ), F ( 9 ) and O ( 10 ) 10, 11, 15–17. In addition, we also found again the very recently reported landomycins S, T and V ( 5 – 7 ) 12…”

Section: Introductionmentioning

confidence: 99%

11-Deoxylandomycinone and landomycins X-Z, new cytotoxic angucyclin(on)es from a Streptomyces cyanogenus K62 mutant strain

et al. 2010

View full text Add to dashboard Cite

Four new angucyclin(on)es, 11-deoxylandomycinone (1) and landomycins X-Z (2–4) were isolated from the crude extract of Streptomyces cyanogenus K62 mutant strain, along with the recently reported landomycins S, T and V (5–7) and five other known compounds. The structures of the new compounds 1–4 were elucidated by 1D and 2D NMR studies along with HRMS analyses. Unique about the structures is that the fourth sugar moiety (sugar D) in landomycins X-Z (2–4) was β-D-amicetose instead of β-D-olivose usually found in this position. The new angucyclin(on)es were biologically evaluated in comparison with previously known congeners against a small panel of MCF-7 (estrogen responsive) and MDA 231 (estrogen refractory) breast cancer cell lines. 11-deoxylandomycinone (IC50 2.1 and 1.2 μM) and landomycin Y (IC50 1.0 and 2.0 μM) showed the highest cytotoxic potencies against both cell lines.

show abstract

“…The structure of the product was further confirmed by comparison of its 1 H and 13 C NMR data with those reported for rabelomycin (see Supporting Information). 3,7 The production of rabelomycin was completely abolished when either acetyl-CoA or malonyl-CoA was removed from the enzyme mixture. These in vitro results were in contrast to earlier in vivo experiments, where the combined heterologous expression of the jadomycin minimal PKS (encoded by jadABC ), the PKS-associated KR (encoded by jadE ), and one cyclase (encoded by jadD ) in Streptomyces lividans TK64 still produced partly cyclized compounds.…”

mentioning

confidence: 99%