Reevaluation of the final steps in the biosynthesis of blasticidin S by Streptomyces griseochromogenes and identification of a novel self-resistance mechanism

Qibo Zhang, Martha C. Cone, Steven J. Gould, Mark Zabriskie

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)693-701
Number of pages9
JournalTetrahedron
Volume56
Issue number5
StatePublished - Jan 28 2000
Externally publishedYes

Fingerprint

Biosynthesis
Streptomyces
Acetyltransferases
Methylation
Reentry
Nucleosides
Leucine
Bacteria
Anti-Bacterial Agents
blasticidin S
demethylblasticidin S

Keywords

  • Amino acids and derivatives
  • Antifungals
  • Biosynthesis
  • Nucleosides

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Reevaluation of the final steps in the biosynthesis of blasticidin S by Streptomyces griseochromogenes and identification of a novel self-resistance mechanism. / Zhang, Qibo; Cone, Martha C.; Gould, Steven J.; Zabriskie, Mark.

In: Tetrahedron, Vol. 56, No. 5, 28.01.2000, p. 693-701.

Research output: Contribution to journalArticle

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