Novel Acetyl-CoA Transfer Route in Saccharomyces Cerevisiae

Acetyl-coenzyme A (acetyl-CoA) is not only an essential intermediate in central metabolism, but also an important precursor for a range of commercially interesting chemicals that can be used as pharmaceuticals, chemical building blocks, or biofuels. In Baker’s yeast Saccharomyces cerevisiae, acetyl-CoA is compartmentalized and not direct interchangeable between the different compartments. Using either the acetyl-carnitine or glyoxylate shuttle, acetyl-CoA produced in peroxisomes or the cytoplasm can, however, be transported into the cytoplasm or the mitochondria, respectively. However, whether acetyl-CoA generated in the mitochondria can be exported to the cytoplasm is still unclear. In the current study we found a mechanism for the transfer of acetyl-CoA from mitochondria to the cytoplasm. We further characterized this novel metabolic route using genetic and biochemical approaches. The results will increase our fundamental understanding of intracellular transport of acetyl units, and hereby enable development of better microbial cell factories that can be used for production of many kinds of acetyl-CoA derived products.