Production of nikkomycins B-x and B-z by mutasynthesis with genetically engineered Streptomyces tendae TU901

Citation
C. Bormann et al., Production of nikkomycins B-x and B-z by mutasynthesis with genetically engineered Streptomyces tendae TU901, J ANTIBIOT, 52(2), 1999, pp. 102-108
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Microbiology
Journal title
JOURNAL OF ANTIBIOTICS
ISSN journal
0021-8820 → ACNP
Volume
52
Issue
2
Year of publication
1999
Pages
102 - 108
Database
ISI
SICI code
0021-8820(199902)52:2<102:PONBAB>2.0.ZU;2-U
Abstract
The previously described Streptomyces tendae nikC::aph mutant was used to m uta-synthesize nikkomycins B-x and B-z. The mutant is deficient in L-lysine 2-aminotransferase, which transaminates lysine to form piperideine 2-carbo xylate, the precursor of the peptidyl side chain of the biologically active nikkomycins I, J, X, and Z, and is therefore unable to produce these nikko mycins. The mutant accumulates the biologically inactive biosynthetic nucle oside precursors nikkomycins C-x and C-z. Resting cell cultures of the muta nt fed with benzoic acid produced the biologically active nikkomycins B-x a nd B-z, which contain 2-amino-4-hydroxy-3-methyl-4-(4'-hydroxyphenyl)butano ic acid as the peptidyl side chain. The structures of nikkomycins B-x and B -z were confirmed by mass spectrometry and NMR. Nikkomycins B-x and B-z exh ibit significantly higher pH stability than their analogues nikkomycins X a nd Z.