Aerobic fermentation
Aerobic fermentation or aerobic glycolysis is a metabolic process by which cells metabolize sugars via fermentation in the presence of oxygen and occurs through the repression of normal respiratory metabolism. Preference of aerobic fermentation over aerobic respiration is referred to as the Crabtree effect in yeast, and is part of the Warburg effect in tumor cells. While aerobic fermentation does not produce adenosine triphosphate in high yield, it allows proliferating cells to convert nutrients such as glucose and glutamine more efficiently into biomass by avoiding unnecessary catabolic oxidation of such nutrients into carbon dioxide, preserving carbon-carbon bonds and promoting anabolism.
Aerobic fermentation in yeast
Aerobic fermentation evolved independently in at least three yeast lineages. It has also been observed in plant pollen, trypanosomatids, mutated E. coli, and tumor cells. Crabtree-positive yeasts will respire when grown with very low concentrations of glucose or when grown on most other carbohydrate sources. The Crabtree effect is a regulatory system whereby respiration is repressed by fermentation, except in low sugar conditions. When Saccharomyces cerevisiae is grown below the sugar threshold and undergoes a respiration metabolism, the fermentation pathway is still fully expressed, while the respiration pathway is only expressed relative to the sugar availability. This contrasts with the Pasteur effect, which is the inhibition of fermentation in the presence of oxygen and observed in most organisms.The evolution of aerobic fermentation likely involved multiple successive molecular steps, which included the expansion of hexose transporter genes, copy number variation and differential expression in metabolic genes, and regulatory reprogramming. Research is still needed to fully understand the genomic basis of this complex phenomenon. Many Crabtree-positive yeast species are used for their fermentation ability in industrial processes in the production of wine, beer, sake, bread, and bioethanol. Through domestication, these yeast species have evolved, often through artificial selection, to better fit their environment. Strains evolved through mechanisms that include interspecific hybridization, horizontal gene transfer, gene duplication, pseudogenization, and gene loss.
Origin of Crabtree effect in yeast
Approximately 100 million years ago, within the yeast lineage there was a whole genome duplication. A majority of Crabtree-positive yeasts are post-WGD yeasts. It was believed that the WGD was a mechanism for the development of the Crabtree effect in these species due to the duplication of alcohol dehydrogenase encoding genes and hexose transporters. However, recent evidence has shown that aerobic fermentation originated before the WGD and evolved as a multi-step process, potentially aided by the WGD. The origin of aerobic fermentation, or the first step, in Saccharomyces Crabtree-positive yeasts likely occurred in the interval between the ability to grow under anaerobic conditions, horizontal transfer of anaerobic DHODase, and the loss of respiratory chain Complex I. A more pronounced Crabtree effect, the second step, likely occurred near the time of the WGD event. Later evolutionary events that aided in the evolution of aerobic fermentation are better understood and outlined in the section discussing the genomic basis of the Crabtree effect.Driving forces
It is believed that a major driving force in the origin of aerobic fermentation was its simultaneous origin with modern fruit. These fruits provided an abundance of simple sugar food source for microbial communities, including both yeast and bacteria. Bacteria, at that time, were able to produce biomass at a faster rate than the yeast. Producing a toxic compound, like ethanol, can slow the growth of bacteria, allowing the yeast to be more competitive. However, the yeast still had to use a portion of the sugar it consumes to produce ethanol. Crabtree-positive yeasts also have increased glycolytic flow, or increased uptake of glucose and conversion to pyruvate, which compensates for using a portion of the glucose to produce ethanol rather than biomass. Therefore, it is believed that the original driving force was to kill competitors. This is supported by research that determined the kinetic behavior of the ancestral ADH protein, which was found to be optimized to make ethanol, rather than consume it.Further evolutionary events in the development of aerobic fermentation likely increased the efficiency of this lifestyle, including increased tolerance to ethanol and the repression of the respiratory pathway. In high sugar environments, S. cerevisiae outcompetes and dominants all other yeast species, except its closest relative Saccharomyces paradoxus. The ability of S. cerevisiae to dominate in high sugar environments evolved more recently than aerobic fermentation and is dependent on the type of high-sugar environment. Other yeasts' growth is dependent on the pH and nutrients of the high-sugar environment.