FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1994706871> ?p ?o ?g. }

• W1994706871 endingPage "1614" @default.
• W1994706871 startingPage "1606" @default.
• W1994706871 abstract "Mithramycin is an aureolic acid-type antimicrobial and antitumor agent produced by Streptomyces argillaceus. Modifying post-polyketide synthase (PKS) tailoring enzymes involved in the production of mithramycin is an effective way of gaining further information regarding the late steps of its biosynthetic pathway. In addition, new “unnatural” natural products of the aureolic acid-type class are likely to be produced. The role of two such post-PKS tailoring enzymes, encoded by mtmC and mtmTIII, was investigated, and four novel aureolic acid class drugs, two premithramycin-type molecules and two mithramycin derivatives, were isolated from mutant strains constructed by insertional gene inactivation of either of these two genes. From data bank comparisons, the corresponding proteins MtmC and MtmTIII were believed to act as a C-methyltransferase involved in the production of the d-mycarose (sugar E) of mithramycin and as a ketoreductase seemingly involved in the biosynthesis of the mithramycin aglycon, respectively. However, gene inactivation and analysis of the accumulated products revealed that both genes encode enzymes participating in the biosynthesis of the d-mycarose building block. Furthermore, the inactivation of MtmC seems to affect the ketoreductase responsible for 4-ketoreduction of sugar C, a d-olivose. Instead of obtaining premithramycin and mithramycin derivatives with a modified E-sugar upon inactivation of mtmC, compounds were obtained that completely lack the E-sugar moiety and that possess an unexpected 4-ketosugar moiety instead of the d-olivose at the beginning of the lower deoxysaccharide chain. The inactivation of mtmTIII led to the accumulation of 4E-ketomithramycin, showing that this ketoreductase is responsible for the 4-ketoreduction of the d-mycarose moiety. The new compounds of the mutant strains, 4A-ketopremithramycin A2, 4A-keto-9-demethylpremithramycin A2, 4C-keto-demycarosylmithramycin, and 4E-ketomithramycin, indicate surprising substrate flexibility of post-PKS enzymes of the mithramycin biosynthetic pathway. Although the glycosyltransferase responsible for the attachment of d-mycarose cannot transfer the unmethylated sugar to the existing lower disaccharide chain, it can transfer the 4-ketoform of sugar E. In addition, the glycosyltransferase MtmGIV, which is responsible for the linkage of sugar C, is also able to transfer an activated 4-ketosugar. The oxygenase MtmOIV, normally responsible for the oxidative cleavage of the tetracyclic premithramycin B into the tricyclic immediate precursor of mithramycin, can act on a substrate analogue with a modified or even incomplete trisaccharide chain. The same is true for glycosyltransferases MtmGI and MtmGII, both of which partake in the formation and attachment of the A-B disaccharide in mithramycin." @default.
• W1994706871 created "2016-06-24" @default.
• W1994706871 creator A5006136698 @default.
• W1994706871 creator A5012452779 @default.
• W1994706871 creator A5013602987 @default.
• W1994706871 creator A5022789546 @default.
• W1994706871 creator A5035685830 @default.
• W1994706871 creator A5059026894 @default.
• W1994706871 creator A5060926002 @default.
• W1994706871 creator A5063129265 @default.
• W1994706871 creator A5065285576 @default.
• W1994706871 creator A5078520712 @default.
• W1994706871 date "2002-01-30" @default.
• W1994706871 modified "2023-10-16" @default.
• W1994706871 title "Ketopremithramycins and Ketomithramycins, Four New Aureolic Acid-Type Compounds Obtained upon Inactivation of Two Genes Involved in the Biosynthesis of the Deoxysugar Moieties of the Antitumor Drug Mithramycin by <i>Streptomyces </i><i>A</i><i>rgillaceus</i>, Reveal Novel Insights into Post-PKS Tailoring Steps of the Mithramycin Biosynthetic Pathway" @default.
• W1994706871 cites W1566248384 @default.
• W1994706871 cites W1965987734 @default.
• W1994706871 cites W1971966571 @default.
• W1994706871 cites W1973801914 @default.
• W1994706871 cites W1976645394 @default.
• W1994706871 cites W1993427900 @default.
• W1994706871 cites W1994789711 @default.
• W1994706871 cites W2011534230 @default.
• W1994706871 cites W2025739622 @default.
• W1994706871 cites W2025831554 @default.
• W1994706871 cites W2029759479 @default.
• W1994706871 cites W2040061443 @default.
• W1994706871 cites W2043524410 @default.
• W1994706871 cites W2043622051 @default.
• W1994706871 cites W2051428034 @default.
• W1994706871 cites W2054073204 @default.
• W1994706871 cites W2058729985 @default.
• W1994706871 cites W2059615514 @default.
• W1994706871 cites W2068092599 @default.
• W1994706871 cites W2069621527 @default.
• W1994706871 cites W2075568163 @default.
• W1994706871 cites W2075867996 @default.
• W1994706871 cites W2081082262 @default.
• W1994706871 cites W2081686208 @default.
• W1994706871 cites W2081724759 @default.
• W1994706871 cites W2091583465 @default.
• W1994706871 cites W2103749241 @default.
• W1994706871 cites W2109502348 @default.
• W1994706871 cites W2124106662 @default.
• W1994706871 cites W2124997867 @default.
• W1994706871 cites W2128565716 @default.
• W1994706871 cites W2134571400 @default.
• W1994706871 cites W2142925821 @default.
• W1994706871 cites W2143524323 @default.
• W1994706871 cites W2146496903 @default.
• W1994706871 cites W2149763977 @default.
• W1994706871 cites W2152511390 @default.
• W1994706871 cites W2158443257 @default.
• W1994706871 cites W2159087794 @default.
• W1994706871 cites W2161090160 @default.
• W1994706871 cites W2170138004 @default.
• W1994706871 cites W2183831760 @default.
• W1994706871 cites W2394961877 @default.
• W1994706871 cites W2465754735 @default.
• W1994706871 cites W2952043277 @default.
• W1994706871 doi "https://doi.org/10.1021/ja0105156" @default.
• W1994706871 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4480631" @default.
• W1994706871 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11853433" @default.
• W1994706871 hasPublicationYear "2002" @default.
• W1994706871 type Work @default.
• W1994706871 sameAs 1994706871 @default.
• W1994706871 citedByCount "65" @default.
• W1994706871 countsByYear W19947068712012 @default.
• W1994706871 countsByYear W19947068712013 @default.
• W1994706871 countsByYear W19947068712014 @default.
• W1994706871 countsByYear W19947068712015 @default.
• W1994706871 countsByYear W19947068712016 @default.
• W1994706871 countsByYear W19947068712019 @default.
• W1994706871 countsByYear W19947068712020 @default.
• W1994706871 countsByYear W19947068712021 @default.
• W1994706871 countsByYear W19947068712022 @default.
• W1994706871 countsByYear W19947068712023 @default.
• W1994706871 crossrefType "journal-article" @default.
• W1994706871 hasAuthorship W1994706871A5006136698 @default.
• W1994706871 hasAuthorship W1994706871A5012452779 @default.
• W1994706871 hasAuthorship W1994706871A5013602987 @default.
• W1994706871 hasAuthorship W1994706871A5022789546 @default.
• W1994706871 hasAuthorship W1994706871A5035685830 @default.
• W1994706871 hasAuthorship W1994706871A5059026894 @default.
• W1994706871 hasAuthorship W1994706871A5060926002 @default.
• W1994706871 hasAuthorship W1994706871A5063129265 @default.
• W1994706871 hasAuthorship W1994706871A5065285576 @default.
• W1994706871 hasAuthorship W1994706871A5078520712 @default.
• W1994706871 hasBestOaLocation W19947068712 @default.
• W1994706871 hasConcept C104317684 @default.
• W1994706871 hasConcept C181199279 @default.
• W1994706871 hasConcept C185592680 @default.
• W1994706871 hasConcept C2776568683 @default.
• W1994706871 hasConcept C2777763344 @default.
• W1994706871 hasConcept C2778635478 @default.
• W1994706871 hasConcept C2779920670 @default.
• W1994706871 hasConcept C36857842 @default.
• W1994706871 hasConcept C523546767 @default.

• next