The effect of sinefungin on the biosynthesis of ganefromycin. Structures of ganefromycins δ1–4

Pearce, Cedric J.; West, Robert R.; Carter, Guy T.

doi:10.1016/0040-4039(95)00149-7

Cited by 8 publications

(9 citation statements)

References 9 publications

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“…[388][389][390][391][392][393][394][395][396][397][398][399][400][401] For 228 and some other congeners it was shown that the activity relies on an inhibition of elongation factor Tu (EF-Tu), [402][403][404][405][406] which plays a key role in protein biosynthesis by mediating the entry of aminoacyl-tRNAs into the ribosome. [407][408][409] For this reason, the name elfamycins was proposed for this compound family.…”

Section: Kirromycinmentioning

confidence: 99%

“…386,387 is a member of a larger family of structurally related compounds (229)(230)(231)(232)(233)(234)(235)(236)(237)(238)(239)(240)(241)(242)(243)(244)(245)(246)(247)(248), many of which exhibit narrow-spectrum activity against Gram-positive bacteria. [388][389][390][391][392][393][394][395][396][397][398][399][400][401] For 228 and some other congeners it was shown that the activity relies on an inhibition of elongation factor Tu (EF-Tu), [402][403][404][405][406] which plays a key role in protein biosynthesis by mediating the entry of aminoacyl-tRNAs into the ribosome. [407][408][409] For this reason, the name elfamycins was proposed for this compound family.…”

Section: Thailandamidesmentioning

confidence: 99%

“…The post-PKS steps in the biosynthesis of ganefromycins 234-237 were investigated in studies by Carter and coworkers. 394,415 When the methyltransferase inhibitor sinefungin was added to cultures of the producer Streptomyces lydicus, a series of new ganefromycins was produced that lacked the O-methyl group at C13. 394 In addition, some compounds carried only a single unmethylated sugar unit, suggesting that the glycosyltransferase(s) that add further sugars recognizes only methylated precursors.…”

Section: Thailandamidesmentioning

confidence: 99%

“…394,415 When the methyltransferase inhibitor sinefungin was added to cultures of the producer Streptomyces lydicus, a series of new ganefromycins was produced that lacked the O-methyl group at C13. 394 In addition, some compounds carried only a single unmethylated sugar unit, suggesting that the glycosyltransferase(s) that add further sugars recognizes only methylated precursors. Another approach used by these researchers consisted of generating random mutants of the producer strain by treatment with the mutagenizing agent N-methyl-N 0 -nitro-Nnitrosoguanidine.…”

Section: Thailandamidesmentioning

confidence: 99%

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Biosynthesis of polyketides by trans-AT polyketide synthases

2010

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Section: Kirromycinmentioning

confidence: 99%

Section: Thailandamidesmentioning

confidence: 99%

Section: Thailandamidesmentioning

confidence: 99%

Section: Thailandamidesmentioning

confidence: 99%

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Biosynthesis of polyketides by trans-AT polyketide synthases

2010

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“…The four O -methyl and four C -methyl groups of 8 were shown to originate from methionine . Later studies demonstrated that the methylation inhibitor sinefungin inhibited the production of 8 and caused accumulation of des- O -methyl intermediates, suggesting that O -methylation is crucial for complete biosynthesis of 8 . The origin of the phenacyl and the trisaccharide units has not been established, and the sequence of elaboration of the ganefromycin aglycon to the ultimate antibiotic also remained unknown.…”

mentioning

confidence: 99%

Biosynthesis of Ganefromycin: Results from Blocked Mutants and Bioconversion Experiments

McDonald¹,

Lotvin²,

Bailey³

et al. 1998

J. Nat. Prod.

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The biosynthetic pathway of ganefromycin alpha (8) was investigated using blocked mutants of Streptomyces lydicus spp. tanzanius, the ganefromycin alpha producer, in conjunction with bioconversion experiments with the products of these mutants. Compounds 1-7 and 9-15, which are structurally related to ganefromycin alpha, were produced by cultures of secretor mutants showing blockage or diminished production of 8. These compounds were isolated, characterized, and subjected to bioconversion experiments using converter and other secretor mutants. Some of the compounds were shown to be products resulting from blocks at various stages in the biosynthetics pathway beyond construction of the polyketide skeleton (e.g., furan ring closure, hydroxylation, glycosylation, etc.). Other compounds were not bioconverted by biosynthetically capable mutants and were deemed shunt products. A mutant's metabolites and bioconverting ability were used to surmise the location of the block. A picture of the later sequence of events leading to the synthesis of ganefromycin alpha emerged, including C23-hydroxylation, C13a-O-methylation, C21a-hydroxylation, and C21a-O-glycosylation. Some of the later steps in the biosynthetic pathway for ganefromycin alpha are proposed.

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