Posttranscriptional regulation of glutamate dehydrogenase 2 and phosphoenolpyruvate carboxykinase in Komagataella phaffii

Dey, T and Rangarajan, PN (2022) Posttranscriptional regulation of glutamate dehydrogenase 2 and phosphoenolpyruvate carboxykinase in Komagataella phaffii. In: Yeast .

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Abstract

The yeast Komagataella phaffii (a.k.a. Pichia pastoris) harbours a unique glutamate utilization pathway in which the cytosolic enzymes glutamate dehydrogenase 2 (GDH2), aspartate aminotransferase 2 (AAT2) and phosphoenolpyruvate carboxykinase (PEPCK) catalyze the sequential conversion of glutamate to α-ketoglutarate, oxaloacetate and phosphoenolpyruvate respectively. GDH2 and PEPCK are essential for glutamate catabolism. Their synthesis is induced by autophagy during carbon starvation and are essential for cell survival. Here, we demonstrate that GDH2 and PEPCK reciprocally regulate each other's protein levels during glutamate catabolism such that GDH2 is downregulated in �pepck and PEPCK is downregulated in �gdh2. We further demonstrate that sequential conversion of glutamate to α-ketoglutarate and oxaloacetate by GDH2 and AAT2, respectively, is essential for PEPCK synthesis in cells metabolizing glutamate. Our studies indicate that translation of GDH2 mRNA is induced by glutamate while oxaloacetate derived from glutamate is likely to be the inducer of PEPCK mRNA translation during glutamate catabolism. Thus, GDH2- and PEPCK-catalyzed reactions are essential for ATP generation and gluconeogenesis respectively during carbon starvation and glutamate catabolism in K. phaffii. We conclude that K. phaffii harbours a unique translational regulatory circuit in which substrates of GDH2 and PEPCK act as inducers of their synthesis, a phenomenon not reported in any yeast species. © 2022 John Wiley & Sons Ltd.

Item Type:	Journal Article
Publication:	Yeast
Publisher:	John Wiley and Sons Ltd
Additional Information:	The copyright for this article belongs to John Wiley and Sons Ltd
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	18 May 2022 09:28
Last Modified:	18 May 2022 09:28
URI:	https://eprints.iisc.ac.in/id/eprint/71842

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