Influence of glycerol and ornithine feeding on clavulanic acid production by Streptomyces clavuligerus

Abstract

-The influence of glycerol and ornithine feeding on clavulanic acid (CA) production by Streptomyces clavuligerus was investigated. In batch experiments, CA maximum concentration (Cp max ) ranged randomly from 430 to 560 mg.L -1 , with a maximum increase of 10% in relation to the control run, without ornithine. However, the maximum volumetric productivity of CA (Pp max ) of 13.7 mg.L -1 .h -1 was obtained with 0.66 g.L -1 of ornithine, 44.2% higher than the Pp max in the control run. In fed-batch experiments, Cp max varied within the narrow range from 1.254 to 1.405 g.L -1 , 2.5 times higher than that obtained in the control run. The presence of ornithine increased the Pp max , although it influenced only slightly the Cp max . Concerning glycerol, the highest CA production of 1.6 g.L -1 was obtained in the fed-batch with glycerol and ornithine (180 and 3.7 g.L −1 ) in a 10-L bioreactor, showing a positive effect of ornithine and glycerol, in the proper proportion (48.6:1), on CA biosynthesis.

Production of clavulanic acid and cephamycin C by Streptomyces clavuligerus under different fed-batch conditions

“…found by Teodoro et al (2010) using cultures of S. clavuligerus ATCC 27064, which is the highest value ever published in the literature for a wild strain. However, Teodoro et al (2010) fed their cultures with glycerol and ornithine, and used soybean protein isolate as nitrogen source, without the carbohydrates present in soybean meal that can inhibit CA production.…”

“…In the batch culture (control run) that used glycerol as carbon source (B1), the maximum levels of production of CephC and CA were similar to or higher than those obtained using fed-batch culture with starch feeding. The production of CA in fed-batch cultures has been widely reported in the literature (Chen et al, 2002(Chen et al, , 2003Mayer and Deckwer, 1996;Teodoro et al, 2006Teodoro et al, , 2010. On the other hand, there is only one work reporting CephC production in fed-batch culture with a wild strain of S. clavuligerus, in which a maltose-fed culture of S. clavuligerus showed a 2-fold reduction in deacetoxycephalosporin C synthase (DAOCS) activity and CephC production, compared to a control run without maltose feeding (Rollins et al, 1988a).…”

“…Teodoro et al (2006) studied the effect of feed medium glycerol concentration and volumetric flow rate in fed-batch cultures for CA production, and the best experimental conditions were found to be a volumetric flow rate of 0.01 L.h -1 and a feed medium with glycerol concentration of 120 g.L -1 , with production of 719 mg.L -1 of CA. Teodoro et al (2010) obtained a production of 1.6 g.L -1 of CA in fed-batch cultivation with glycerol feeding. Recent work has reported the production of CephC using solid-state fermentation.…”

“…The presence of certain nutrients in the culture medium, such as sources of C, N, P, S, and salts, as well as substances produced in the biosynthetic route, can enhance the production of CA or CephC (Fang and Demain, 1995;Chen et al, 2002, Oliveira et al, 2009. Glycerol, for example, is preferentially used as carbon source for CA production (Chen et al, 2002;Elson and Oliver, 1978;Romero et al, 1984;Teodoro et al, 2006Teodoro et al, , 2010, whereas starch is more suitable for the production of CephC (Lebrihi et al, 1988;Rius and Demain, 1997).…”

Bioconversion from crude glycerin by Xanthomonas campestris 2103: xanthan production and characterization

“…A promising alternative use of this byproduct is the microbial conversion of crude glycerin through biotechnological processes (Johnson and Taconi, 2007;da Silva et al, 2009) into value-added products, like poly-3-hydroxybutyrate polymers (Zhu et al, 2010); clavulanic acid (Teodoro et al, 2010); recombinant human erythropoietin (Elik et al, 2008), and citric acid (Papanikolaou et al, 2002;Rywińska et al, 2011).…”