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.
Weitnauer, G., Hauser, G., Hofmann, C., Linder, U., Boll, R., Pelz, K., … Bechthold, A. (2004). Novel avilamycin derivatives with improved polarity generated by targeted gene disruption. Chemistry and Biology, 11(10), 1403–1411. https://doi.org/10.1016/j.chembiol.2004.08.016