Abstract
The final steps in the biosynthesis of the antifungal peptidyl- nucleoside blasticidin S (3) have been revised to include a novel self- resistance mechanism wherein the previously proposed final precursor, demethylblasticidin S (7), is modified with a leucine residue yielding leucyldemethylblasticidin S (10) which exhibits reduced antibiotic activity. Methylation of 10 yields leucylblasticidin S (9) which can be exported from the bacterium and hydrolyzed to 3. Also disclosed is the finding of a blasticidin S N-acetyltransferase activity that may function to detoxify 3 and 7 inadvertently produced prior to export or which gain reentry to the cell. (C) 2000 Elsevier Science Ltd.
Original language | English (US) |
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Pages (from-to) | 693-701 |
Number of pages | 9 |
Journal | Tetrahedron |
Volume | 56 |
Issue number | 5 |
DOIs | |
State | Published - Jan 28 2000 |
Externally published | Yes |
Keywords
- Amino acids and derivatives
- Antifungals
- Biosynthesis
- Nucleosides
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry