The optimization of medium components for the production of clavulanic acid by Streptomyces clavuligerus was performed using both factional factorial design and response surface methodology. The factional factorial design experiment was initially employed for this purpose and it was found that soy meal powder, FeSO4.7H(2)O, and ornithine were the most important medium components (confidence levels above 85%). Response surface methodology for optimization was further investigated. These three composing elements showed significant effects on producing clavulanic acid. Their optimal concentrations were: soy meal powder 38.102 g/l, FeSO4.7H(2)O 0.395 g/l, and ornithine 1.177 g/l. The yield of clavulanic acid was increased by 50% by culturing strain S. clavuligerus in the nutritionally optimized fermentation medium. (C) 2004 Elsevier Ltd. All rights reserved.