Isolation and structures of T-2636 antibiotics

Harada, Setsuo; Higashide, Eiji; Fugono, Takeshi; Kishi, Toshiharu

doi:10.1016/s0040-4039(01)88131-4

Cited by 47 publications

(38 citation statements)

References 1 publication

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“…LC is a macrocyclic compound composed of a 17-membered carbocyclic ring, bridged by a 6-membered lactone. LM is a macrolide whose 14-member lactone ring is decorated with 4-acetyl-L-arcanose and D-chalcose sugars (29,30) resembling erythromycin (ERY) (Fig. 1).…”

mentioning

confidence: 99%

The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics

Auerbach

Mermershtain

Davidovich

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Crystallographic analysis revealed that the 17-member polyketide antibiotic lankacidin produced by Streptomyces rochei binds at the peptidyl transferase center of the eubacterial large ribosomal subunit. Biochemical and functional studies verified this finding and showed interference with peptide bond formation. Chemical probing indicated that the macrolide lankamycin, a second antibiotic produced by the same species, binds at a neighboring site, at the ribosome exit tunnel. These two antibiotics can bind to the ribosome simultaneously and display synergy in inhibiting bacterial growth. The binding site of lankacidin and lankamycin partially overlap with the binding site of another pair of synergistic antibiotics, the streptogramins. Thus, at least two pairs of structurally dissimilar compounds have been selected in the course of evolution to act synergistically by targeting neighboring sites in the ribosome. These results underscore the importance of the corresponding ribosomal sites for development of clinically relevant synergistic antibiotics and demonstrate the utility of structural analysis for providing new directions for drug discovery.lankamycin | ribosomes | synergism | resistance | rRNA

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confidence: 99%

The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics

Auerbach

Mermershtain

Davidovich

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…1) are unique 17-membered carbocyclic polyketide compounds that are different from the typical even-membered macrolides (macrolactones) (Harada et al, 1969;Uramoto et al, 1969;Harada & Kishi, 1974). The lkc cluster contains one nonribosomal peptide synthetase (NRPS)/polyketide synthase (PKS) hybrid gene (lkcA), three multidomain PKS genes (lkcC, lkcF, and lkcG), an amine oxidase gene (lkcE), and pyrroloquinoline quinone (PQQ) biosynthetic genes (lkcK-lkcO) (Fig.…”

Section: Lankacidin Biosynthesismentioning

confidence: 99%

Characterization of the Biosynthetic Gene Clusters Located on the Streptomyces Linear Plasmid

Arakawa

2010

Actinomycetologica

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“…volubilis (3,5,7,11) have a characteristic 17-membered macrocyclic structure (4)(5)(6)13). They show strong antibacterial activity mainly against gram-positive bacteria (8,11,27).…”

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In vitro and in vivo activities of sedecamycin against Treponema hyodysenteriae

Hayashi

Suenaga

Narukawa

et al. 1988

Antimicrob Agents Chemother

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Sedecamycin (lankacidin A), one of the lankacidin-group antibiotics, showed potent activity against Treponema hyodysenteriae. The MICs of sedecamycin against 79 field isolates of T. hyodysenteriae ranged from 0.78 to 12.5 ,Ig/ml, the MIC for 90% of the strains tested (MIC90) being 3.13 ,ug/ml. The protective and therapeutic effects of sedecamycin were compared with those of carbadox, tiamulin, and lincomycin against experimental infection with T. hyodysenteriae in mice. The protective effect of sedecamycin was similar to that of carbadox, two times more potent than that of tiamulin, and three times greater than that of lincomycin. In the therapeutic test, sedecamycin showed activity similar to that of carbadox and was two times more active than both tiamulin and lincomycin. At doses of 10 mg or more of sedecamycin per kg, the recurrence of shedding of T. hyodysenteriae into the feces of mice was not detected for at least 8 weeks postmedication.

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Isolation and structures of T-2636 antibiotics

Cited by 47 publications

References 1 publication

The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics

The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics

Characterization of the Biosynthetic Gene Clusters Located on the Streptomyces Linear Plasmid

In vitro and in vivo activities of sedecamycin against Treponema hyodysenteriae

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