Carbon source regulation of ACV synthetase inCephalosporium acremonium C-10

Abstract

The high cephalosporin-producing strainCephalosporium acremonium C-10 was found to be still subject to carbon source regulation despite earlier mutations which decreased this effect. Under phosphorus source limitation, a low concentration (2.7%) and a high concentration (6.3%) of glucose or glycerol as carbon source supported similar growth rates. The high concentration of glucose or glycerol decreased β-lactam production and repressed the formation of deacetoxycephalosporin C synthase, but not of isopenicillin N synthase or δ-(l-α-aminoadipyl)-l-cysteinyl-d-valine synthetase. A high concentration of glucose also suppressed penicillin N accumulation; this suggested the existence of an enzyme inhibition effect by glucose or its catabolites. This was supported by data from a resting-cell experiment. In vitro studies showed glucose to inhibit the action of ACV synthetase in crude extracts, with more than 70% of the activity inhibited by 5 mM glucose. Glucose-6-phosphate and glyceraldehyde-3-phosphate also were inhibitory. 3-Phosphoglycerate inhibited expandase activity. Inhibition by glucose and its catabolites of ACV synthetase appears to be one of the mechanisms involved in the negative carbon source regulation of β-lactam biosynthesis.