Quinovosamycins: New tunicamycin-type antibiotics in which the α, β-1',11'-linked N-acetylglucosamine residue is replaced by N-acetylquinovosamine

Neil P.J. Price, David P. Labeda, Todd A. Naumann, Karl E. Vermillion, Michael J. Bowman, Mark A. Berhow, William W. Metcalf, Kenneth M. Bischoff

Research output: Contribution to journalArticlepeer-review

Abstract

Tunicamycins (TUN) are potent inhibitors of polyprenyl phosphate N-acetylhexosamine 1-phosphate transferases (PPHP), including essential eukaryotic GPT enzymes and bacterial HexNAc 1-P translocases. Hence, TUN blocks the formation of eukaryotic N-glycoproteins and the assembly of bacterial call wall polysaccharides. The genetic requirement for TUN production is well-established. Using two genes unique to the TUN pathway (tunB and tunD) as probes we identified four new prospective TUN-producing strains. Chemical analysis showed that one strain, Streptomyces niger NRRL B-3857, produces TUN plus new compounds, named quinovosamycins (QVMs). QVMs are structurally akin to TUN, but uniquely in the 1',11'-HexNAc sugar head group, which is invariably d-GlcNAc for the known TUN, but is d-QuiNAc for the QVM. Surprisingly, this modification has only a minor effect on either the inhibitory or antimicrobial properties of QVM and TUN. These findings have unexpected consequences for TUN/QVM biosynthesis, and for the specificity of the PPHP enzyme family.

Original languageEnglish (US)
Pages (from-to)637-646
Number of pages10
JournalJournal of Antibiotics
Volume69
Issue number8
DOIs
StatePublished - Aug 1 2016

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Fingerprint Dive into the research topics of 'Quinovosamycins: New tunicamycin-type antibiotics in which the α, β-1',11'-linked N-acetylglucosamine residue is replaced by N-acetylquinovosamine'. Together they form a unique fingerprint.

Cite this