A derivative of the glycopeptide A40926 produced by inactivation of the beta-hydroxylase gene in Nonomuraea sp. ATCC39727.
The actinomycete Nonomuraea sp. ATCC39727 produces the glycopeptide A40926. In the corresponding dbv cluster, ORF28 encodes a putative hydroxylase. A gene replacement mutant of ORF28 in Nonomuraea produces a small amount of an A40926-related metabolite, 16 amu smaller than the parent compound, which was identified as the desoxyderivative of A40926 lacking the beta-hydroxyl group on the tyrosine moiety. This result demonstrates that ORF28 is actually involved in the formation of the beta-hydroxytyrosine residue present in A40926. The formation of an altered glycopeptide and the inability to rescue A40926 production upon feeding free beta-hydroxytyrosine are consistent with the possibility that, in contrast to balhimycin formation, hydroxylation occurs after tyrosine activation by the nonribosomal peptide synthetase.
Stinchi
Sofia
S
Vicuron Pharmaceuticals, Gerenzano (VA), Italy.
Carrano
Lucia
L
Lazzarini
Ameriga
A
Feroggio
Marina
M
Grigoletto
Armando
A
Sosio
Margherita
M
Donadio
Stefano
S
D000192:Actinomycetales / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D017353:Gene Deletion; D006900:Hydroxylation; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000502:physiology; D015394:Molecular Structure; D016254:Mutagenesis, Insertional; D017334:Teicoplanin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
C054981:A 40926; D001426:Bacterial Proteins; D014443:Tyrosine; D017334:Teicoplanin; D004295:Dihydroxyphenylalanine; D006899:Mixed Function Oxygenases