TY - JOUR
T1 - Novel avilamycin derivatives with improved polarity generated by targeted gene disruption
AU - Weitnauer, Gabriele
AU - Hauser, Gerd
AU - Hofmann, Carsten
AU - Linder, Ulrike
AU - Boll, Raija
AU - Pelz, Klaus
AU - Glaser, Steffen J.
AU - Bechthold, Andreas
N1 - Funding Information:
This work is dedicated to Prof. Dr. H. G. Floss on the occasion of his 70 th birthday. The work was supported by Combinature Biopharm AG, Berlin, by Bundesministerium für Bildung und Forschung grants to A.B., and by the Fonds der Chemischen Industrie grant to S.J.G. We thank A. Wittmer and A. Schandelmeier for assistance.
PY - 2004/10
Y1 - 2004/10
N2 - The oligosaccharide antibiotics avilamycin A and C are produced by Streptomyces viridochromogenes Tü57. Both consist of a heptasaccharide chain, which is attached to a polyketide-derived dichloroisoeverninic acid moiety. They show excellent antibiotic activity against Gram-positive bacteria. Both molecules are modified by O-methylation at different positions, which contributes to poor water solubility and difficulties in galenical drug development. In order to generate novel avilamycin derivatives with improved polarity and improved pharmacokinetic properties, we generated a series of mutants with one, two, or three mutated methyltransferase genes. Based on the structure of the novel avilamycin derivatives, the exact function of three methyltransferases, AviG2, AviG5, and AviG6, involved in avilamycin biosynthesis could be assigned.
AB - The oligosaccharide antibiotics avilamycin A and C are produced by Streptomyces viridochromogenes Tü57. Both consist of a heptasaccharide chain, which is attached to a polyketide-derived dichloroisoeverninic acid moiety. They show excellent antibiotic activity against Gram-positive bacteria. Both molecules are modified by O-methylation at different positions, which contributes to poor water solubility and difficulties in galenical drug development. In order to generate novel avilamycin derivatives with improved polarity and improved pharmacokinetic properties, we generated a series of mutants with one, two, or three mutated methyltransferase genes. Based on the structure of the novel avilamycin derivatives, the exact function of three methyltransferases, AviG2, AviG5, and AviG6, involved in avilamycin biosynthesis could be assigned.
UR - http://www.scopus.com/inward/record.url?scp=5444251592&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2004.08.016
DO - 10.1016/j.chembiol.2004.08.016
M3 - Article
C2 - 15489167
AN - SCOPUS:5444251592
SN - 1074-5521
VL - 11
SP - 1403
EP - 1411
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 10
ER -