Bioconversion of avermectin into 27-OH avermectin.
The bioconversion of avermectin to its 27-hydroxy derivative is achieved with Nocardia autotrophica subsp. canberrica. The approach of increasing bioconversion productivity rather than efficiency was adopted in these studies. Process improvement studies focused on the physico-chemical conditions of the fermentation, examined initially at the shake-flask scale. Bioconversion yields were affected by pH, substrate concentration, time of substrate addition, substrate solubilization, carbon to nitrogen ratio, and medium strength. Optimization of these parameters resulted in a 8-fold process improvement. During pre scale-up studies, the sensitivity of this bioconversion to the antifoam employed was demonstrated and lard oil was selected as giving the best results. Additional process changes were required during scale-up efforts in larger vessels, including replacement of the original substrate solvent with dimethylsulfoxide.
Chartrain
M
M
Merck and Company, Inc., Rahway, NJ 07065.
White
R
R
Goegelman
R
R
Gbewonyo
K
K
Greasham
R
R
D000871:Anthelmintics / Q000378:metabolism*; D003470:Culture Media; D005285:Fermentation; D006863:Hydrogen-Ion Concentration; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000378:metabolism; D007700:Kinetics; D000432:Methanol / Q000378:metabolism; D015394:Molecular Structure; D009615:Nocardia / Q000378:metabolism*
D000871:Anthelmintics; D003470:Culture Media; C068576:27-hydroxyavermectin; D007559:Ivermectin; C019264:avermectin; D000432:Methanol