Selectively improving nikkomycin Z production by blocking the imidazolone biosynthetic pathway of nikkomycin X and uracil feeding in Streptomyces ansochromogenes

Nikkomycins are a group of peptidyl nucleoside antibiotics and act as potent inhibitors of chitin synthases in fungi and insects. Nikkomycin X and Z are the main components produced by Streptomyces ansochromogenes.

Of them, nikkomycin Z is a promising antifungal agent with clinical significance. Since highly structural similarities between nikkomycin Z and X, separation of nikkomycin Z from the culture medium of S.

ansochromogenes is difficult. Thus, generating a nikkomycin Z selectively producing strain is crucial for scaling up the nikkomycin Z yields for clinical trials.

Results: A nikkomycin Z producing strain (sanPDM) was constructed by blocking the imidazolone biosynthetic pathway of nikkomycin X via genetic manipulation and yielded 300 mg/L nikkomycin Z when the nikkomycin X production was abolished.

To further increase the yield of nikkomycin Z, the effects of different precursors on its production were investigated. Precursors of nucleoside moiety (uracil or uridine) had a stimulatory effect on nikkomycin Z production while precursors of peptidyl moiety (L-lysine and L-glutamate) had no effect.

sanPDM produced the maximum yields of nikkomycin Z (800 mg/L) in the presence of uracil at the concentration of 2 g/L and it was approximately 2.6-fold higher than that of the parent strain.

Conclusion: A nikkomycin Z selectively producing strain was obtained by genetic manipulation combined with precursors feeding .The strategy presented here might be applicable in other bacteria to selectively produce targeted antibiotics.

Author: Guojian LiaoJine LiLei LiHaihua YangYuqing TianHuarong Tan
Credits/Source: Microbial Cell Factories 2009, 8:61

Published on: 2009-11-23

Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please make sure to read our disclaimer prior to contacting 7thSpace Interactive. To contact our editors, visit our online helpdesk. If you wish submit your own press release, click here.

Comments Page 0 of 0

There are currently 0 comments to display.

+ Add New Comment

Custom Search