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

Saudagar and Singhal (2007b) showed that using fed-batch fermentation technologies, production of clavulanic acid could be further increased following batch fermentation that revealed increased production by arginine and threonine.

“Following batch fermentation that revealed increased clavulanic acid production by arginine and threonine, Saudagar and Singhal (2007b) showed that by using fed-batch fermentation technologies; the production of the compound could be further increased.”

Among amino acids tested by Saudagar and Singhal (2007b), the highest clavulanic acid concentration was observed with L-threonine, which was not reported in other literature included in the review.

“Among these amino acids, the highest concentration of clavulanic acid was observed in media supplemented with L-threonine; which was not reported in other literature included in this systematic review.”

The potential repressive effect of phosphate on clavulanic acid production in S. clavuligerus was demonstrated by selected studies.

“The potential repressive effect of phosphate on clavulanic acid production in S. clavuligerus was demonstrated by two selected studies (Lebrihi et al., 1987; Bushell et al., 2006; Saudagar and Singhal, 2007b).”

Saudagar and Singhal (2007b) demonstrated that addition of phosphate in the production medium showed a biphasic response.

“Without changing the pH of the media, Saudagar and Singhal (2007b) demonstrated that the addition of phosphate in the production medium showed a biphasic response.”

From the included studies, one study showed that L-threonine improved clavulanic acid production.

“From the included studies, one study showed that L-threonine improved the production of clavulanic acid (Saudagar and Singhal, 2007b).”

Supplementation of L-threonine prevents anaplerotic flux on pyruvate to synthesize amino acids such as isoleucine, which increases availability of C3 precursors and eventually enhances clavulanic acid production.

“Indeed the supplementation of L-threonine was found to prevent the anaplerotic flux on pyruvate to synthesize amino acids such as isoleucine, which in turn increased the availability of C3 precursors and eventually enhanced clavulanic acid production (Ives and Bushell, 1997; Bushell et al., 2006; Saudagar and Singhal, 2007b).”

Only three studies reported the effect of amino acid in fed-batch fermentation.

“Only three studies reported the effect of amino acid in fed-batch fermentation (Chen et al., 2003; Saudagar and Singhal, 2007b; Teodoro et al., 2010);”