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Applied and Environmental Microbiology, November 2002, p. 5422-5428, Vol. 68, No. 11
0099-2240/02/$04.00+0     DOI: 10.1128/AEM.68.11.5422-5428.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effect of Pyruvate Carboxylase Overexpression on the Physiology of Corynebacterium glutamicum

Mattheos A. G. Koffas, Gyoo Yeol Jung, Juan C. Aon, and Gregory Stephanopoulos^*

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Received 29 April 2002/ Accepted 5 August 2002

Pyruvate carboxylase was recently sequenced in Corynebacterium glutamicum and shown to play an important role of anaplerosis in the central carbon metabolism and amino acid synthesis of these bacteria. In this study we investigate the effect of the overexpression of the gene for pyruvate carboxylase (pyc) on the physiology of C. glutamicum ATCC 21253 and ATCC 21799 grown on defined media with two different carbon sources, glucose and lactate. In general, the physiological effects of pyc overexpression in Corynebacteria depend on the genetic background of the particular strain studied and are determined to a large extent by the interplay between pyruvate carboxylase and aspartate kinase activities. If the pyruvate carboxylase activity is not properly matched by the aspartate kinase activity, pyc overexpression results in growth enhancement instead of greater lysine production, despite its central role in anaplerosis and aspartic acid biosynthesis. Aspartate kinase regulation by lysine and threonine, pyruvate carboxylase inhibition by aspartate (shown in this study using permeabilized cells), as well as well-established activation of pyruvate carboxylase by lactate and acetyl coenzyme A are the key factors in determining the effect of pyc overexpression on Corynebacteria physiology.

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* Corresponding author. Mailing address: Department of Chemical Engineering, MIT, Room 56-469, Cambridge, MA 02139. Phone: (617) 253-4583. Fax: (617) 253-3122. E-mail: gregstep{at}mit.edu.

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Applied and Environmental Microbiology, November 2002, p. 5422-5428, Vol. 68, No. 11
0099-2240/02/$04.00+0     DOI: 10.1128/AEM.68.11.5422-5428.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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