Novel avermectins produced by mutational biosynthesis.
Avermectins with a wide range of novel C-25 substituents have been prepared by feeding carboxylic acids or their biosynthetic precursors to a Streptomyces avermitilis mutant strain ATCC 53568. This organism lacks the ability to form isobutyric and S-2-methylbutyric acids from their 2-oxo acid precursors and thus is unable to produce natural avermectins unless supplied with these acids. The novel avermectins produced by mutational biosynthesis possess broad-spectrum antiparasitic activity.
Dutton
C J
CJ
Central Research Division, Pfizer Ltd., Kent, England.
Gibson
S P
SP
Goudie
A C
AC
Holdom
K S
KS
Pacey
M S
MS
Ruddock
J C
JC
Bu'Lock
J D
JD
Richards
M K
MK
D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002107:Caenorhabditis / Q000187:drug effects; D002264:Carboxylic Acids / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004175:Diptera; D005285:Fermentation; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015394:Molecular Structure; D009154:Mutation; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
D000871:Anthelmintics; D002264:Carboxylic Acids; D007559:Ivermectin; C019264:avermectin