Transketolase Activity in the Formation of the Azinomycin Azabicycle Moiety
The biosynthesis of the azinomycins involves the conversion of glutamic acid to an aziridino[1,2-a]pyrrolidine moiety, which together with the epoxide moiety imparts anticancer activity to these agents. The mechanism of azabicycle formation is complex and involves at least 14 enzymatic steps. Previous research has identified N-acetyl-glutamate 5-semialdehyde as a key intermediate, which originates from protection of the amino terminus of glutamic acid and subsequent reduction of the γ-carboxylate. This study reports on the seminal discovery of a thiamin-dependent transketolase responsible for the formation of 2-acetamido-5,6-dihydroxy-6-oxoheptanoic acid, which accounts for the two-carbon extension needed to complete the carbon framework of the azabicycle moiety.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:58 |
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| Enthalten in: |
Biochemistry - 58(2019), 52 vom: 31. Dez., Seite 5255-5258 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Washburn, Lauren A [VerfasserIn] |
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| Links: |
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| Themen: |
Azabicyclo Compounds |
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| Anmerkungen: |
Date Completed 22.06.2020 Date Revised 22.06.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.biochem.9b00477 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM30034421X |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The biosynthesis of the azinomycins involves the conversion of glutamic acid to an aziridino[1,2-a]pyrrolidine moiety, which together with the epoxide moiety imparts anticancer activity to these agents. The mechanism of azabicycle formation is complex and involves at least 14 enzymatic steps. Previous research has identified N-acetyl-glutamate 5-semialdehyde as a key intermediate, which originates from protection of the amino terminus of glutamic acid and subsequent reduction of the γ-carboxylate. This study reports on the seminal discovery of a thiamin-dependent transketolase responsible for the formation of 2-acetamido-5,6-dihydroxy-6-oxoheptanoic acid, which accounts for the two-carbon extension needed to complete the carbon framework of the azabicycle moiety | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
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| 650 | 7 | |a Transketolase |2 NLM | |
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| 700 | 1 | |a Martinez, Flor |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Rachel P |e verfasserin |4 aut | |
| 700 | 1 | |a Pryor, Kendall |e verfasserin |4 aut | |
| 700 | 1 | |a Rimes, Emily |e verfasserin |4 aut | |
| 700 | 1 | |a Watanabe, Coran M H |e verfasserin |4 aut | |
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