Carbon Catabolite Regulation of Cephalosporin Production in Streptomyces clavuligerus

摘要: Cephalosporin production byStreptomyces clavuligerus isregulated bysome typeofcarbon catabolite control. Increasing concentrations ofpreferred carbon sources,suchasglycerol andmaltose, decreased oftheantibiotics. Poorer sources,such asa-ketoglutarate andsuccinate, ledtohighspecific ofcephalosporins andshifted thedynamics offermentation to a greater degree ofassociation withgrowth. Theresults supporttheconceptthat thephase inwhich aproduct ismadebyamicroorganism isnotafunction ofthe particular molecule produced, butrather ofthenutritional environment presented totheorganism. Thebiosynthetic pathways leading totheproduction ofsecondary metabolites suchasantibiotics areoften connected toandinfluenced by thepathways ofprimary metabolism (4). For example, anendproduct oranintermediate of aprimary pathway frequently serves asaprecursor fortheantibiotic molecule. Suchintermediates orendproducts could bepartofa biosynthetic, amphibolic, orcatabolic pathway. Catabolic involving energy metabolismoftheorganism areunder strict control in microorganisms. Whenafavored carbon/energy source isused, thecell isusually prevented from producing enzymes whichcatabolize other carboncompounds. Itispossible that suchacatabolic regulatory mechanism also theproduction metabolites. The strong influence ofcarbon sources ontheproduction ofantibiotics hasbeenreported inseveral cases (3). Ourinterest hasbeenfocused onStreptomyces ctavuligerus, whichwasfirst described byHiggensandKastner (6). Thisstrain produces four ,8-lactam antibiotics (2,7,11): twoofthese arecephalosporins [7-(5-amino-5-carboxyvaleramido)-3-carbamoyloxymethyl-3-cephem-4-carboxylic acidand7-(5-amino-5-carboxyvaleramido)- 7-methoxy-3 -carbamoyloxymethyl