Diauxie

Diauxie

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Diauxie is a French word coined by Jacques Monod
Jacques Monod
Jacques Lucien Monod was a French biologist who was awarded a Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and Andre Lwoff "for their discoveries concerning genetic control of enzyme and virus synthesis"...

 to mean two growth phases. The word is used in English in cell biology
Cell biology
Cell biology is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...

 to describe the growth phases of a microorganism
Microorganism
A microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...

 in batch culture as it metabolizes
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 a mixture of two sugars. Rather than metabolizing the two available sugars simultaneously, microbial cells commonly consume them in a sequential pattern, resulting in two separate growth phases.
During the first phase, cells preferentially metabolize the sugar on which it can grow faster (often glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 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.

Jacques Monod
Jacques Monod
Jacques Lucien Monod was a French biologist who was awarded a Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and Andre Lwoff "for their discoveries concerning genetic control of enzyme and virus synthesis"...

 discovered diauxic growth in 1941 during his experiments with Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...

and Bacillus subtilis
Bacillus subtilis
Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium commonly found in soil. A member of the genus Bacillus, B. subtilis is rod-shaped, and has the ability to form a tough, protective endospore, allowing the organism to tolerate...

. 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. Even in the first two panels (a and b of the Figure 1), the sugars are consumed sequentially with no diauxic lag. Focusing on the well defined diauxic growth of E. coli on the mixture of glucose and lactose
Lactose
Lactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...

, his later work led to the lac operon
Lac operon
The lac operon is an operon required for the transport and metabolism of lactose in Escherichia coli and some other enteric bacteria. It consists of three adjacent structural genes, lacZ, lacY and lacA. The lac operon is regulated by several factors including the availability of glucose and of...

 model of gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...

 and subsequently a Nobel prize.

Diauxie occurs because organisms use operons or multiple sets of genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...

 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
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

, 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
Lactococcus lactis
Lactococcus lactis is a Gram-positive bacterium used extensively in the production of buttermilk and cheese, but has recently also become famous as the first genetically modified organism to be used alive for the treatment of human disease. L...

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
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...

 Saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...

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
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 fermentation
Fermentation (biochemistry)
Fermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. In contrast, respiration is where electrons are donated to an exogenous electron acceptor, such as oxygen,...

 to aerobic respiration even though aerobic respiration is the more efficient pathway to grow on glucose. Contrary to the more commonly invoked Pasteur effect
Pasteur effect
The Pasteur effect is an inhibiting effect of oxygen on the fermentation process.-Discovery:The effect was discovered in 1857 by Louis Pasteur, who showed that aerating yeasted broth causes yeast cell growth to increase, while conversely, fermentation rate decreases.-Explanation:The effect can be...

, this phenomenon of preferring the faster growth supporting fermentation is closer to the Warburg effect
Warburg effect
The phrase "Warburg effect" is used for two unrelated observations in biochemistry, one in plant physiology and the other in oncology, both due to Nobel laureate Otto Heinrich Warburg.-Plant physiology:...

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

Mechanism


In the 1940s, Monod hypothesized that a single enzyme could adapt to metabolize different sugars. It took 15 years of further work to show that this was incorrect. During his work on the lac operon
Lac operon
The lac operon is an operon required for the transport and metabolism of lactose in Escherichia coli and some other enteric bacteria. It consists of three adjacent structural genes, lacZ, lacY and lacA. The lac operon is regulated by several factors including the availability of glucose and of...

 of E. coli, Joshua Lederberg
Joshua Lederberg
Joshua Lederberg ForMemRS was an American molecular biologist known for his work in microbial genetics, artificial intelligence, and the United States space program. He was just 33 years old when he won the 1958 Nobel Prize in Physiology or Medicine for discovering that bacteria can mate and...

 isolated β-galactosidase and found it in greater quantities in colonies grown on lactose compared to other sugars. Melvin Cohn in Monod's lab at the Pasteur Institute then found that β-galactosides induced enzyme activity. The idea of enzyme adaptation was thus replaced with the concept of enzyme induction, in which a molecule induces expression of a gene or operon, often by binding to a repressor protein and preventing it from attaching to the operator.

In the case of the bacterial diauxic shift from glucose to lactose metabolism, glucose initially inhibits the ability of the enzyme adenylate cyclase
Adenylate cyclase
Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....

 to synthesize cyclic AMP (cAMP). cAMP, in turn, is required for the catabolite activator protein
Catabolite Activator Protein
Catabolite Activator Protein or CAP is a transcriptional activator that exists as a homodimer in solution, with each subunit comprising a ligand-binding domain at the N-terminus , which is also responsible for the dimerization of the protein, and a DNA-binding domain at the C-terminus...

 (CAP) to bind to DNA and activate the transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

 of the lac operon, which includes genes necessary for lactose metabolism. The presence of lactose is sensed through the activity of the lac repressor
Lac repressor
The lac repressor is a DNA-binding protein which inhibits the expression of genes coding for proteins involved in the metabolism of lactose in bacteria. These genes are repressed when lactose is not available to the cell, ensuring that the bacterium only invests energy in the production of...

, which inhibits transcription of the lac operon unless it is bound by lactose. Thus, if glucose is present, cAMP levels remain low, so CAP is unable to activate transcription of the lac operon, regardless of the presence or absence of lactose. Upon the exhaustion of the glucose supply, cAMP levels rise, allowing CAP to activate the genes necessary for the metabolism of other food sources, including lactose if it is present.