Influence of feeding conditions on clavulanic acid production in fed-batch cultivation with medium containing glycerol

Abstract

First, the effect of different levels of nitrogen source on clavulanic acid (CA) production was evaluated in batch cultivations utilizing complex culture medium containing glycerol and three different levels of soy protein isolate (SPI). Cellular growth, evaluated in terms of the rheological parameter K, was highest with a SPI concentration of 30 g.L(-1) (4.42 g.L(-1) N total). However, the highest production of CA (380 mg.L(-1)) was obtained when an intermediate concentration of 20 g.L(-1) of SPI (2.95 g.L(-1) total N) was used. To address this, the influences of volumetric flow rate (F) and glycerol concentration in the complex feed medium (Cs(F)) in fed-batch cultivations were investigated. The best experimental condition for CA production was F=0.01 L.h(-1) and Cs(F)=120 g.L(-1), and under these conditions maximum CA production was practically twice that obtained in the batch cultivation. A single empirical equation was proposed to relate maximum CA production with F and Cs(F) in fed-batch experiments.

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

“…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).…”

“…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).…”

“…Saudagar and Singhal (2007) studied the effect of glycerol feeding on CA production by S. clavuligerus in shake flasks, and observed an increase of 18% in CA production compared to the control. 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.…”

Determinação Do Ph E Temperatura Ótimos Para a Produtividade Do Ácido Clavulânico Utilizando O Streptomyces Clavuligerus Atcc 27064

“…As Tabelas 1 e 2 apresentam a composição do meio de reativação, crescimento e produção, respectivamente (ROSA et al, 2005;TEODORO et al, 2006 …”

Detection of Acetyl Monoglyceride as a Metabolite of Newly Isolated Glycerol-assimilating Bacteria

“…The conversion of glycerol by biotransformation has been extensively studied, and many possible products, including 1,3-propandiol 5,6) , ethanol and hydrogen gas 7) , 3-hydroxypropionaldehyde 8) , dihydroxyacetone (DHA) 9) , clavulanic acid 10) , poly(hydroxyalkanoate) 11) , biosurfactants 12) , and lipids 13) , have been developed. There are also many reports of other glycerol metabolites such as 2,3-butanediol, lactate, and acetate 14) .…”