The cytosolic pathway of L-malic acid synthesis in Saccharomyces cerevisiae: the role of fumarase

Applied Microbiology and Biotechnology
O PinesI Goldberg

Abstract

Saccharomyces cerevisiae accumulates L-malic acid but not only minute amounts of fumaric acid. A 13C-nuclear magnetic resonance study following the label from glucose to L-malic acid indicates that the L-malic acid is synthesized from pyruvic acid via oxaloacetic acid. From this, and from previously published studies, we conclude that a cytosolic reductive pathway leading from pyruvic acid via oxaloacetic acid to L-malic acid is responsible for the L-malic acid production in yeast. The non-production of fumaric acid can be explained by the conclusion that, in the cell, cytosolic fumarase catalyzes the conversion of fumaric acid to L-malic but not the reverse. This conclusion is based on the following findings. (a) The cytosolic enzyme exhibits a 17-fold higher affinity towards fumaric acid than towards L-malic acid; the Km for L-malic acid is very high indicating that L-malic acid is not an in vivo substrate of the enzyme. (b) Overexpression of cytosolic fumarase does not cause accumulation of fumaric acid (but rather more L-malic acid). (c) According to 13C NMR studies there is no interconversion of cytosolic L-malic and fumaric acids.

References

May 13, 1977·Archives of Microbiology·S Haarasilta, L Taskinen
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Dec 1, 1994·Archives of Biochemistry and Biophysics·K I Minard, L McAlister-Henn
Jul 1, 1986·Applied and Environmental Microbiology·W KenealyI Goldberg
May 1, 1991·Biotechnology and Bioengineering·E BattatI Goldberg

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Citations

Mar 19, 2011·Applied Biochemistry and Biotechnology·Yueyue DingHe Huang
Oct 21, 2005·The Journal of Molecular Diagnostics : JMD·N Afrina AlamTodd Weaver
Jun 13, 2003·Current Genetics·H VolschenkM Viljoen-Bloom
Jan 13, 2016·Applied Microbiology and Biotechnology·Sha LiWeifeng Lin
May 12, 2012·Journal of Bioscience and Bioengineering·Shunichi NakayamaAtsumi Nakazato
Aug 5, 2015·Metabolic Engineering·Xiulai ChenLiming Liu
Dec 29, 2007·Metabolic Engineering·W A de Jongh, J Nielsen
Mar 6, 2010·The Plant Journal : for Cell and Molecular Biology·Itsara PracharoenwattanaSteven M Smith
Oct 13, 2006·Experimental Cell Research·Sharon KarnielyOphry Pines
May 28, 2013·Metabolic Engineering·Xiulai ChenJian Chen
Sep 4, 2012·Biotechnology Advances·Qing XuJianping Wen
Jan 1, 2012·Computational and Structural Biotechnology Journal·Ping Liu, Laura R Jarboe
Nov 26, 2010·Applied and Environmental Microbiology·X ZhangL O Ingram
Mar 28, 2020·Applied Microbiology and Biotechnology·Xi ZhangYu Deng

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