Propionate metabolism in Saccharomyces cerevisiae: implications for the metabolon hypothesis.
Aerobic, glucose-limited chemostat of Saccharomyces cerevisiae CBS 8066 co-metabolized propionate when this compound was added to the reservoir medium. Co-metabolism of propionate led to an increase of the biomass and protein yields. Attempts to grow S. cerevisiae on propionate as a sole source of carbon and energy were not successful. Activities of propionyl-CoA synthetase in cell-free extracts were sufficient to account for the rates of propionate consumption observed in the chemostat cultures. Activities of propionyl-CoA carboxylase, a key enzyme of the methylmalonyl-CoA pathway of propionate metabolism, were negligible. In contrast, activities of 2-methylcitrate synthase, a key enzyme activity of the 2-methylcitrate pathway of propionate metabolism, increased substantially with increasing propionate-to-glucose ratios in the reservoir media, and were sufficient to account for the propionate consumption rates observed in the chemostat cultures. This suggested that the 2-methylcitrate pathway is the major pathway of propionate metabolism in S. cerevisiae. In the literature, labelling patterns observed after incubation of this yeast with [3-13C]propionate have been interpreted as evidence for channelling of tricarboxylic acid (TCA) cycle intermediates, possibly as a consequence of the organization of TCA cycle enzymes in a metabolon. However, this interpretation of 13C-labelling patterns rested on the assumption that propionate metabolism in S. cerevisiae occurs via the methylmalonyl-CoA pathway. Since the distribution of 13C in alanine reported in the literature is fully compatible with a major role of the 2-methylcitrate pathway in propionate metabolism, it cannot be interpreted as evidence for the existence of a TCA cycle metabolon in S. cerevisiae.
Pronk
J T
JT
Department of Microbiology and Enzymology, Kluyver Laboratory of Biotechnology, Delft University of Technology, The Netherlands.
van der Linden-Beuman
A
A
Verduyn
C
C
Scheffers
W A
WA
van Dijken
J P
JP
D000106:Acetate-CoA Ligase / Q000378:metabolism; D002262:Carboxy-Lyases / Q000378:metabolism; D002951:Citrates / Q000378:metabolism; D004734:Energy Metabolism; D005656:Fungal Proteins / Q000378:metabolism; D043586:Methylmalonyl-CoA Decarboxylase; D008954:Models, Biological; D011422:Propionates / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
D002951:Citrates; D005656:Fungal Proteins; D011422:Propionates; C031605:2-methylcitric acid; D002262:Carboxy-Lyases; D000106:Acetate-CoA Ligase; D043586:Methylmalonyl-CoA Decarboxylase; C029658:propionic acid