Optimization of nutritional requirements and feeding strategies for clavulanic acid production by Streptomyces clavuligerus

The present work reports the nutritional requirements and environmental conditions for submerged culture of Streptomyces clavuligerus for clavulanic acid production using orthogonal matrix method (Taguchi L-16 design) and also fed-batch fermentation for clavulanic acid production by feeding glycerol, arginine and threonoine to the fermentation medium intermittently. Clavulanic acid production was increased by 18% with the span of feeding glycerol and reached a maximum at 1.30 mg/ml with 120 h glycerol feeding as compared to 1.10 mg/ml in the control. The production also increased with the span of feeding amino acids and reached a maximum of 1.31 and 1.86 mg/ml with feeding arginine and threonine, respectively in 120 h. There was an overall increase of 18% and 9% in clavulanic acid production with arginine and threonine feeding as compared to the respective controls (1.10 and 1.70 mg/ml, respectively). (c) 2006 Elsevier Ltd. All rights reserved.