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n a similar way to carbon, the nitrogen source is under-stood to regulate secondary metabolism.Actinomycete isopenicillin synthase wasfound to be sensitive to ammonium levels (Demain, 1986).However, Zhang et al. (1996) found ammonium to stimu-late an antibiotic produced by Streptomyces griseofuocus.Control of ammonia concentration during the mid-cyclewas found to be important in the optimization of idiophasesecondary metabolite production (Junker et al., 1998),though this may reflect the role of nitrogen in growth pro-motion.The use of unsuitable amino acids as a nitrogen sourcecan inhibit good synthesis of secondary metabolites(Ahronowitz, 1980; Martain and Demain, 1980).Multi-input feed strategiesmay be of use in process intensification, after optimizationof the nitrogen type and concentration at different fermen-tation stages
n a similar way to carbon, the nitrogen source is under-stood to regulate secondary metabolism. High nitrogen lev-els have been noted to repress iodophase production ofantibiotics (for example, see reviews by Ahronowitz, 1980;Martain and Demain, 1980; Doull and Vining, 1990; Spizekand Tichy, 1995). Actinomycete isopenicillin synthase wasfound to be sensitive to ammonium levels (Demain, 1986).However, Zhang et al. (1996) found ammonium to stimu-late an antibiotic produced by Streptomyces griseofuocus.Control of ammonia concentration during the mid-cyclewas found to be important in the optimization of idiophasesecondary metabolite production (Junker et al., 1998),though this may reflect the role of nitrogen in growth pro-motion.The use of unsuitable amino acids as a nitrogen sourcecan inhibit good synthesis of secondary metabolites(Ahronowitz, 1980; Martain and Demain, 1980). Con-versely, specific amino acids can, in some cases, enhanceantibiotic production. The addition of cystine, for example,increases the phenazine-1-carboxylic acid yield in Pseudo-monas fluorescens (Slininger and Jackson, 1992), and me-thionene is well known for its stimulatory effect on cepha-losporin C biosynthesis, when added during the growthphase of Cephalosporium acremonium (Martain and De-main, 1980). These effects may be due to a specific aminoacid interacting with the regulation of secondary metabolicpathways. Again, as for carbon, little is known about theeffect of amino acid concentration or type on antibioticsynthesis in marine bacteria. Multi-input feed strategiesmay be of use in process intensification, after optimizationof the nitrogen type and concentration at different fermen-tation stages
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