Diauxic growth

Diauxic growth, diauxie or diphasic growth is any cell growth characterized by cellular growth in two phases. Diauxic growth, meaning double growth, is caused by the presence of two substrates (usually sugars) in a culture growth media, when the microbial cells are capable of faster growth on one of these substrates. The faster-growth supporting substrate is consumed first, which leads to rapid growth, followed by a lag phase. During the lag phase the cellular machinery used to metabolize the second (slower-growth supporting) substrate is activated and subsequently the second substrate is metabolized.

This can also occur when the bacterium in a closed batch culture consumes most of its nutrients and is entering the stationary phase when new nutrients are suddenly added to the growth media. The bacterium enters a lag phase where it tries to ingest the food. Once the food starts being utilized, it enters a new log phase showing a second peak on the growth curve.

Jacques Monod discovered diauxic growth in 1941 during his experiments with Escherichia coli and Bacillus subtilis. While growing these bacteria on various combination of sugars during his doctoral thesis research, Monod observed that often two distinct growth phases are clearly visible in batch culture, as seen in Figure 1.

During the first phase, cells preferentially metabolize the sugar on which it can grow faster (often glucose but not always). Only after the first sugar has been exhausted do the cells switch to the second. At the time of the "diauxic shift", there is often a lag period during which cells produce the enzymes needed to metabolize the second sugar.

Monod continued his work on the underlying mechanism for his observations on diauxic growth and proposed the lac operon model of gene expression, which led to a Nobel prize.

Diauxie occurs because organisms use operons or multiple sets of genes to control differently the expression of enzymes needed to metabolize the different nutrients or sugars they encounter. If an organism allocates its energy and other resources (e.g. amino acids) to synthesize enzymes needed to metabolize a sugar that can only support a slower growth rate and not use all or most of its available resources to synthesize the enzymes that metabolize a different sugar providing a faster growth rate, such an organism will be at a reproductive disadvantage compared to those that choose to grow on the faster growth supporting sugar. Through evolution, organisms have developed the ability to regulate their genetic control mechanisms so as to only express those genes resulting in the fastest growth rate. For example, when grown in the presence of both glucose and maltose, Lactococcus lactis will produce enzymes to metabolize glucose first, altering its gene expression to use maltose only after the supply of glucose has been exhausted.

In the case of the baker's or brewer's yeast Saccharomyces cerevisiae growing on glucose with plenty of aeration, the diauxic growth pattern is commonly observed in batch culture. During the first growth phase, when there is plenty of glucose and oxygen available, the yeast cells prefer glucose fermentation to aerobic respiration, in a phenomenon known as aerobic fermentation. Although aerobic respiration may seem a more energetically-efficient pathway (higher cell mass yield per glucose consumed) to grow on glucose, fermentation is the faster pathway for the yeast cells to growth (i.e. higher growth rate) and hence preferred. Contrary to the more commonly invoked Pasteur effect, this phenomenon is closer to the Warburg effect observed in faster growing tumors.

The intracellular genetic regulatory mechanisms have evolved to enforce this choice, as fermentation provides a faster anabolic growth rate for the yeast cells than the aerobic respiration of glucose, which favors catabolism. After glucose is depleted, the fermentative product ethanol is oxidised in a noticeably slower second growth phase, if oxygen is available.