Generation of novel landomycins M and O through targeted gene disruption

被引:39
作者
Luzhetskyy, A
Zhu, LL
Gibson, M
Fedoryshyn, M
Dürr, C
Hofmann, C
Hoffmeister, D
Ostash, B
Mattingly, C
Adams, V
Fedorenko, V
Rohr, J
Bechthold, A
机构
[1] Univ Freiburg, Inst Pharmazeut Wissensch, D-79104 Freiburg, Germany
[2] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA
[3] Lvov Natl Univ, Dept Genet & Biotechnol, UA-79005 Lvov, Ukraine
[4] Univ Kentucky, Coll Pharm, Dept Pharm Practice & Sci, Lexington, KY 40536 USA
关键词
antitumor agents; biosynthesis; glycosylation; hydroxylation; landomycin;
D O I
10.1002/cbic.200400316
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Two genes from Streptomyces cyanogenous S 136 that encode the reductose LonZ4 and the hydroxylose LonZ5, which are involved in landomycin A biosynthesis, were characterized by targeted gene inactivation. Analyses of the corresponding mutants as well as complementation experiments have allowed us to show that LanZ4 and LanZ5 are responsible for the unique C-11-hydroxylation that occurs during landomycin biosynthesis. Compounds accumulated by the lanZ4/Z5 mutants are the previously described landomycin F and the new landomycins M and O.
引用
收藏
页码:675 / 678
页数:4
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