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Deletion of the Glucose-6-Phosphate Dehydrogenase Gene KlZWF1 Affects both Fermentative and Respiratory Metabolism in Kluyveromyces lactis

Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Roma La Sapienza, Piazzale Aldo Moro 5, 00185 Rome, Italy,¹ Dipartimento di Genetica, Antropologia e Evoluzione, Parco Area delle Scienze 11-A, Università degli Studi di Parma, 43100 Parma, Italy,² Dipartimento di Medicina Sperimentale e Patologia, Università di Roma La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy³

Received 16 June 2006/ Accepted 26 October 2006

In Kluyveromyces lactis, the pentose phosphate pathway is an alternative route for the dissimilation of glucose. The first enzyme of the pathway is the glucose-6-phosphate dehydrogenase (G6PDH), encoded by KlZWF1. We isolated this gene and examined its role. Like ZWF1 of Saccharomyces cerevisiae, KlZWF1 was constitutively expressed, and its deletion led to increased sensitivity to hydrogen peroxide on glucose, but unlike the case for S. cerevisiae, the Klzwf1 strain had a reduced biomass yield on fermentative carbon sources as well as on lactate and glycerol. In addition, the reduced yield on glucose was associated with low ethanol production and decreased oxygen consumption, indicating that this gene is required for both fermentation and respiration. On ethanol, however, the mutant showed an increased biomass yield. Moreover, on this substrate, wild-type cells showed an additional band of activity that might correspond to a dimeric form of G6PDH. The partial dimerization of the G6PDH tetramer on ethanol suggested the production of an NADPH excess that was negative for biomass yield.

Published ahead of print on 3 November 2006.