FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912221660> ?p ?o ?g. }

• W2912221660 endingPage "477" @default.
• W2912221660 startingPage "468" @default.
• W2912221660 abstract "To combat the increasing spread of antimicrobial resistance and the shortage of novel anti-infectives, one strategy for the development of new antibiotics is to optimize known chemical scaffolds. Here, we focus on the biosynthetic engineering of Amycolatopsis sulphurea for derivatization of the atypical tetracycline chelocardin and its potent broad-spectrum derivative 2-carboxamido-2-deacetyl-chelocardin. Heterologous biosynthetic genes were introduced into this chelocardin producer to modify functional groups and generate new derivatives. We demonstrate cooperation of chelocardin polyketide synthase with tailoring enzymes involved in biosynthesis of oxytetracycline from Streptomyces rimosus. An interesting feature of chelocardin, compared with oxytetracycline, is the opposite stereochemistry of the C4 amino group. Genes involved in C4 transamination and N,N-dimethylation of oxytetracycline were heterologously expressed in an A. sulphurea mutant lacking C4-aminotransferase. Chelocardin derivatives with opposite stereochemistry of the C4 amino group, as N,N-dimethyl- epi-chelocardin and N,N-dimethyl-2-carboxamido-2-deacetyl- epi-chelocardin, were produced only when the aminotransferase from oxytetracycline was coexpressed with the N-methyltransferase OxyT. Surprisingly, OxyT exclusively accepted intermediates carrying an S-configured amino group at C4 in chelocardin. Applying medicinal chemistry approaches, several 2-carboxamido-2-deacetyl- epi-chelocardin derivatives modified at C4 were produced. Analysis of the antimicrobial activities of the modified compounds demonstrated that the primary amine in the R configuration is a crucial structural feature for activity of chelocardin. Unexpectedly, C10 glycosylated chelocardin analogues were identified, thus revealing the glycosylation potential of A. sulphurea. However, efficient glycosylation of the chelocardin backbone occurred only after engineering of a dimethylated amino group at the C4 position in the opposite S configuration, which suggests some evolutionary remains of chelocardin glycosylation." @default.
• W2912221660 created "2019-02-21" @default.
• W2912221660 creator A5003741128 @default.
• W2912221660 creator A5008265235 @default.
• W2912221660 creator A5016977199 @default.
• W2912221660 creator A5019312327 @default.
• W2912221660 creator A5029006834 @default.
• W2912221660 creator A5042159463 @default.
• W2912221660 creator A5044079805 @default.
• W2912221660 creator A5057933985 @default.
• W2912221660 creator A5063773972 @default.
• W2912221660 creator A5075091004 @default.
• W2912221660 creator A5077818118 @default.
• W2912221660 creator A5085526664 @default.
• W2912221660 date "2019-02-12" @default.
• W2912221660 modified "2023-10-16" @default.
• W2912221660 title "Engineering Atypical Tetracycline Formation in <i>Amycolatopsis sulphurea</i> for the Production of Modified Chelocardin Antibiotics" @default.
• W2912221660 cites W1903959420 @default.
• W2912221660 cites W1967778128 @default.
• W2912221660 cites W1967872471 @default.
• W2912221660 cites W1981252549 @default.
• W2912221660 cites W2000234746 @default.
• W2912221660 cites W2005294016 @default.
• W2912221660 cites W2011534230 @default.
• W2912221660 cites W2013651533 @default.
• W2912221660 cites W2028008678 @default.
• W2912221660 cites W2030631206 @default.
• W2912221660 cites W2038368740 @default.
• W2912221660 cites W2044707490 @default.
• W2912221660 cites W2045313092 @default.
• W2912221660 cites W2053878100 @default.
• W2912221660 cites W2083116540 @default.
• W2912221660 cites W2088851175 @default.
• W2912221660 cites W2103794549 @default.
• W2912221660 cites W2113790776 @default.
• W2912221660 cites W2117747794 @default.
• W2912221660 cites W2120600651 @default.
• W2912221660 cites W2128880918 @default.
• W2912221660 cites W2132387742 @default.
• W2912221660 cites W2146157756 @default.
• W2912221660 cites W2156737450 @default.
• W2912221660 cites W2159865967 @default.
• W2912221660 cites W2160161888 @default.
• W2912221660 cites W2162987252 @default.
• W2912221660 cites W2166673123 @default.
• W2912221660 cites W2167089027 @default.
• W2912221660 cites W2296672537 @default.
• W2912221660 cites W2324805309 @default.
• W2912221660 cites W2387392928 @default.
• W2912221660 cites W2488467722 @default.
• W2912221660 cites W2531329626 @default.
• W2912221660 cites W2531568206 @default.
• W2912221660 cites W2613613983 @default.
• W2912221660 cites W2766707489 @default.
• W2912221660 cites W4230425360 @default.
• W2912221660 cites W4233143487 @default.
• W2912221660 doi "https://doi.org/10.1021/acschembio.8b01125" @default.
• W2912221660 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30747520" @default.
• W2912221660 hasPublicationYear "2019" @default.
• W2912221660 type Work @default.
• W2912221660 sameAs 2912221660 @default.
• W2912221660 citedByCount "20" @default.
• W2912221660 countsByYear W29122216602020 @default.
• W2912221660 countsByYear W29122216602021 @default.
• W2912221660 countsByYear W29122216602022 @default.
• W2912221660 countsByYear W29122216602023 @default.
• W2912221660 crossrefType "journal-article" @default.
• W2912221660 hasAuthorship W2912221660A5003741128 @default.
• W2912221660 hasAuthorship W2912221660A5008265235 @default.
• W2912221660 hasAuthorship W2912221660A5016977199 @default.
• W2912221660 hasAuthorship W2912221660A5019312327 @default.
• W2912221660 hasAuthorship W2912221660A5029006834 @default.
• W2912221660 hasAuthorship W2912221660A5042159463 @default.
• W2912221660 hasAuthorship W2912221660A5044079805 @default.
• W2912221660 hasAuthorship W2912221660A5057933985 @default.
• W2912221660 hasAuthorship W2912221660A5063773972 @default.
• W2912221660 hasAuthorship W2912221660A5075091004 @default.
• W2912221660 hasAuthorship W2912221660A5077818118 @default.
• W2912221660 hasAuthorship W2912221660A5085526664 @default.
• W2912221660 hasConcept C104317684 @default.
• W2912221660 hasConcept C143065580 @default.
• W2912221660 hasConcept C181199279 @default.
• W2912221660 hasConcept C185592680 @default.
• W2912221660 hasConcept C2776671240 @default.
• W2912221660 hasConcept C2778635478 @default.
• W2912221660 hasConcept C2780681812 @default.
• W2912221660 hasConcept C501593827 @default.
• W2912221660 hasConcept C553450214 @default.
• W2912221660 hasConcept C55493867 @default.
• W2912221660 hasConcept C71240020 @default.
• W2912221660 hasConceptScore W2912221660C104317684 @default.
• W2912221660 hasConceptScore W2912221660C143065580 @default.
• W2912221660 hasConceptScore W2912221660C181199279 @default.
• W2912221660 hasConceptScore W2912221660C185592680 @default.
• W2912221660 hasConceptScore W2912221660C2776671240 @default.
• W2912221660 hasConceptScore W2912221660C2778635478 @default.
• W2912221660 hasConceptScore W2912221660C2780681812 @default.
• W2912221660 hasConceptScore W2912221660C501593827 @default.

• next