Molecular characterization of co-transcribed genes from Streptomyces tendae Tu901 involved in the biosynthesis of the peptidyl moiety of the peptidylnucleoside antibiotic nikkomycin

Citation
C. Bruntner et al., Molecular characterization of co-transcribed genes from Streptomyces tendae Tu901 involved in the biosynthesis of the peptidyl moiety of the peptidylnucleoside antibiotic nikkomycin, MOL G GENET, 262(1), 1999, pp. 102-114
Citations number
58
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MOLECULAR AND GENERAL GENETICS
ISSN journal
0026-8925 → ACNP
Volume
262
Issue
1
Year of publication
1999
Pages
102 - 114
Database
ISI
SICI code
0026-8925(199908)262:1<102:MCOCGF>2.0.ZU;2-1
Abstract
Six genes (nikA, nikB, nikD, nikE, nikF, and nikG) from Streptomyces tendae Tu901 were identified by sequencing the region surrounding the nikC gene, which encodes L-lysine 2-aminotransferase, previously shown to catalyze the initial reaction in the biosynthesis of hydroxypyridylhomothreonine, the p eptidyl moiety of the peptidyl nucleoside antibiotic nikkomycin. These gene s, together with the nikC gene, span a DNA region of 7.87 kb and are transc ribed as a polycistronic mRNA in a growth-phase-dependent manner. The seque nces of the deduced proteins NikA and NikB exhibit significant similarity t o those of acetaldehyde dehydrogenases and 4-hydroxy-2-oxovalerate aldolase s, respectively, which are involved in meta-cleavage degradation of aromati c hydrocarbons. The predicted NikD gene product shows sequence similarity t o monomeric sarcosine oxidases, and the deduced NikE protein belongs to the superfamily of adenylate-forming enzymes. The nikF gene and the nikC gene encode a cytochrome P450 monooxygenase and a ferredoxin, respectively. Disr uption of any of the genes nikA, nikB, nikD, nikE and nikF by insertion of a kanamycin resistance cassette abolished formation of the biologically act ive nikkomycins I, J, X, and Z. The nikA. nikB. nikD. and nikE mutants accu mulated the nucleoside moieties nikkomycins C-x and C-z. In the nikD and ni kE mutants nikkomycin production (nikkomycins I, J, X, Z) could be restored by feeding with picolinic acid and hydroxypyridylhomothreonine, respective ly. The nikF mutant exclusively produced novel derivatives, nikkomycins L-x and L-z, which contain pyridylhomothreonine as the peptidyl moiety. Our re sults indicate that the nikA, nikB, nikD, nikE, nikF, and nikG genes, in ad dition to nikC, function in the biosynthetic pathway leading to hydroxypyri dylhomothreonine; the putative activities of each of their products are dis cussed.