Fermentation

Fermentationis a type ofredoxmetabolismcarried out in the absence ofoxygen.During fermentation,organic molecules(e.g.,glucose) arecatabolizedand donateelectronsto other organic molecules. In the process,ATPand organic end products (e.g.,lactate) are formed.
Because oxygen is not required, it is an alternative toaerobic respiration. Over 25% ofbacteriaandarchaeacarry out fermentation.They live in thegut,sediments,food, and other environments. Eukaryotes, including humans and other animals, also carry out fermentation.
Fermentation is important in several areas of human society.Humans have used fermentation in production of food for 13,000 years.Humansand theirlivestockhave microbes in the gut that carry out fermentation, releasing products used by the host for energy.Fermentation is used at anindustrial levelto produce commodity chemicals, such asethanoland lactate.  In total, fermentation forms more than 50 metabolic end productsThis process highlights the power of microbial activity.
The definition of fermentation has evolved over the years.The most modern definition is catabolism, where organic compounds are both the electron donor and acceptor.A common electron donor isglucose, andpyruvateis a common electron acceptor. This definition distinguishes fermentation fromaerobic respiration, where oxygen is the acceptor and types ofanaerobic respiration, where an inorganic species is the acceptor.
Fermentation had been defined differently in the past. In 1876,Louis Pasteurdescribed it as "la vie sans air" (life without air).This definition came before the discovery of anaerobic respiration. Later, it had been defined as catabolism that forms ATP through onlysubstrate-level phosphorylation.However, several pathways of fermentation have been discovered to form ATP through anelectron transport chainandATP synthase, also.
Some sources define fermentation loosely as any large-scale biological manufacturing process.SeeIndustrial fermentation. This definition focuses on the process of manufacturing rather than metabolic details.
Fermentation is used by organisms to generate ATP energy for metabolism.One advantage is that it requires no oxygen or other external electron acceptors, and thus it can be carried out when those electron acceptors are absent.  A disadvantage is that it produces relatively little ATP, yielding only between 2 and 4.5 per glucosecompared to 32 for aerobic respiration.
Over 25% ofbacteriaandarchaeacarry out fermentation.This type of metabolism is most common in the phylumBacillota, and it is least common inActinomycetota.Their most common habitat is host-associated ones, such as the gut.
Animals, including humans, also carry out fermentation.The product of fermentation in humans is lactate, and it is formed duringanaerobic exerciseor incancerous cells.  No animal is known to survive on fermentation alone, even as one parasitic animal (Henneguya zschokkei) is known to survive without oxygen.
Fermentation uses a range of substrates and forms a variety of metabolic end products.  Of the 55 end products formed, the most common areacetateandlactate.Of the 46 chemically-defined substrates that have been reported, the most common are glucose and other sugars.
When an organic compound is fermented, it is broken down to a simpler molecule and releases electrons.  The electrons are transferred to a redoxcofactor, which in turn transfers them to an organic compound.ATPis generated in the process, and it can be formed by substrate-levelphosphorylationor byATP synthase.
When glucose is fermented, it entersglycolysisor thepentose phosphate pathwayand is converted topyruvate.From pyruvate, pathways branch out to form a number of end products (e.g. lactate). At several points, electrons are released and accepted by redox cofactors (NADandferredoxin). At later points, these cofactors donate electrons to their final acceptor and become oxidized. ATP is also formed at several points in the pathway.
While fermentation is simple in overview, its details are more complex.  Across organisms, fermentation of glucose involves over 120 different biochemical reactions.Further, multiple pathways can be responsible for forming the same product. For forming acetate from its immediate precursor (pyruvate oracetyl-CoA), six separate pathways have been found.
In ethanol fermentation, one glucose molecule is converted into two ethanol molecules and twocarbon dioxide(CO2) molecules.It is used to make bread dough rise: the carbon dioxide forms bubbles, expanding the dough into a foam.The ethanol is the intoxicating agent in alcoholic beverages such as wine, beer and liquor.Fermentation of feedstocks, includingsugarcane,maize, andsugar beets, produces ethanol that is added togasoline.In some species of fish, includinggoldfishandcarp, it provides energy when oxygen is scarce (along with lactic acid fermentation).
Before fermentation, a glucose molecule breaks down into two pyruvate molecules (glycolysis). The energy from thisexothermic reactionis used to bind inorganicphosphatesto ADP, which converts it to ATP, and convert NADto NADH. The pyruvates break down into twoacetaldehydemolecules and give off two carbon dioxide molecules as waste products. The acetaldehyde is reduced into ethanol using the energy and hydrogen from NADH, and the NADH is oxidized into NADso that the cycle may repeat. The reaction is catalyzed by the enzymes pyruvate decarboxylase and alcohol dehydrogenase.
The history of ethanol as a fuel spans several centuries and is marked by a series of significant milestones.Samuel Morey, an American inventor, was the first to produce ethanol by fermenting corn in 1826. However, it was not until theCalifornia Gold Rushin the 1850s that ethanol was first used as a fuel in the United States.Rudolf Dieseldemonstrated his engine, which could run on vegetable oils and ethanol, in 1895, but the widespread use of petroleum-based diesel engines made ethanol less popular as a fuel. In the 1970s, the oil crisis reignited interest in ethanol, and Brazil became a leader in ethanol production and use. The United States began producing ethanol on a large scale in the 1980s and 1990s as a fuel additive to gasoline, due to government regulations. Today, ethanol continues to be explored as a sustainable and renewable fuel source, with researchers developing new technologies and biomass sources for its production.
Homolactic fermentation(producing only lactic acid) is the simplest type of fermentation. Pyruvate from glycolysisundergoes a simple redox reaction, forminglactic acid.Overall, one molecule of glucose (or any six-carbon sugar) is converted to two molecules of lactic acid:
It occurs in the muscles of animals when they need energy faster than thebloodcan supply oxygen. It also occurs in some kinds ofbacteria(such aslactobacilli) and somefungi. It is the type of bacteria that convertlactoseinto lactic acid inyogurt, giving it its sour taste. These lactic acid bacteria can carry out eitherhomolactic fermentation, where the end-product is mostly lactic acid, orheterolactic fermentation, where some lactate is further metabolized to ethanol and carbon dioxide(via thephosphoketolasepathway), acetate, or other metabolic products, e.g.:
If lactose is fermented (as in yogurts and cheeses), it is first converted into glucose and galactose (both six-carbon sugars with the same atomic formula):
Heterolactic fermentation is in a sense intermediate betweenlactic acid fermentationand other types, e.g.alcoholic fermentation. Reasons to go further and convert lactic acid into something else include:
Hydrogengas is produced in many types of fermentation as a way to regenerate NADfrom NADH.Electronsare transferred toferredoxin, which in turn is oxidized byhydrogenase, producing H2.Hydrogen gas is asubstrateformethanogensandsulfate reducers, which keep the concentration of hydrogen low and favor the production of such an energy-rich compound,but hydrogen gas at a fairly high concentration can nevertheless be formed, as inflatus.
For example,Clostridium pasteurianumferments glucose tobutyrate,acetate, carbon dioxide, and hydrogen gas:The reaction leading to acetate is:
Glyoxylate fermentation is a type of fermentation used by microbes that are able to utilize glyoxylate as a nitrogen source.
Other types of fermentation includemixed acid fermentation,butanediol fermentation,butyrate fermentation,caproate fermentation, andacetone–butanol–ethanol fermentation.
In food and industrial contexts, any chemical modification performed by a living being in a controlled container can be termed "fermentation". The following do not fall into the biochemical sense, but are called fermentation in the larger sense:
Fermentation can be used to make alternative protein sources. It is commonly used to modify existing protein foods, including plant-based ones such as soy, into more flavorful forms such astempehandfermented tofu.
More modern "fermentation" makesrecombinant proteinto help producemeat analogue,milk substitute,cheese analogues, andegg substitutes. Some examples are:
Heme proteinssuch as myoglobin andhemoglobingive meat its characteristic texture, flavor, color, and aroma. The myoglobin and leghemoglobin ingredients can be used to replicate this property, despite them coming from a vat instead of meat.
Industrial fermentationcan be used for enzyme production, where proteins with catalytic activity are produced and secreted by microorganisms. The development of fermentation processes, microbial strain engineering and recombinant gene technologies has enabled the commercialization of a wide range of enzymes.Enzymesare used in all kinds of industrial segments, such as food (lactose removal, cheese flavor), beverage (juice treatment), baking (bread softness, dough conditioning), animal feed, detergents (protein, starch and lipid stain removal), textile, personal care and pulp and paper industries.
Mostindustrial fermentationuses batch or fed-batch procedures, although continuous fermentation can be more economical if various challenges, particularly the difficulty of maintaining sterility, can be met.
In a batch process, all the ingredients are combined and the reactions proceed without any further input. Batch fermentation has been used for millennia to make bread and alcoholic beverages, and it is still a common method, especially when the process is not well understood.However, it can be expensive because the fermentor must be sterilized using high pressure steam between batches.Strictly speaking, there is often addition of small quantities of chemicals to control the pH or suppress foaming.
Batch fermentation goes through a series of phases. There is a lag phase in which cells adjust to their environment; then a phase in which exponential growth occurs. Once many of the nutrients have been consumed, the growth slows and becomes non-exponential, but production ofsecondary metabolites(including commercially important antibiotics and enzymes) accelerates. This continues through a stationary phase after most of the nutrients have been consumed, and then the cells die.
Fed-batch fermentation is a variation of batch fermentation where some of the ingredients are added during the fermentation. This allows greater control over the stages of the process. In particular, production of secondary metabolites can be increased by adding a limited quantity of nutrients during the non-exponential growth phase. Fed-batch operations are often sandwiched between batch operations.
The high cost of sterilizing the fermentor between batches can be avoided using various open fermentation approaches that are able to resist contamination. One is to use a naturally evolved mixed culture. This is particularly favored in wastewater treatment, since mixed populations can adapt to a wide variety of wastes.Thermophilicbacteria can produce lactic acid at temperatures of around 50 °Celsius, sufficient to discourage microbial contamination; and ethanol has been produced at a temperature of 70 °C. This is just below its boiling point (78 °C), making it easy to extract.Halophilicbacteria can produce bioplastics in hypersaline conditions. Solid-state fermentation adds a small amount of water to a solid substrate; it is widely used in the food industry to produce flavors, enzymes and organic acids.
In continuous fermentation, substrates are added and final products removed continuously.There are three varieties:chemostats, which hold nutrient levels constant;turbidostats, which keep cell mass constant; andplug flow reactorsin which the culture medium flows steadily through a tube while the cells are recycled from the outlet to the inlet.If the process works well, there is a steady flow of feed and effluent and the costs of repeatedly setting up a batch are avoided. Also, it can prolong the exponential growth phase and avoid byproducts that inhibit the reactions by continuously removing them. However, it is difficult to maintain a steady state and avoid contamination, and the design tends to be complex.Typically the fermentor must run for over 500 hours to be more economical than batch processors.
The use of fermentation, particularly forbeverages, has existed since theNeolithicand has been documented dating from 7000 to 6600 BCE inJiahu,China,5000 BCE inIndia,Ayurvedamentions many Medicated Wines, 6000 BCE in Georgia,3150 BCE inancient Egypt,3000 BCE inBabylon,2000 BCE in pre-Hispanic Mexico,and 1500 BC inSudan.Fermented foods have a religious significance inJudaismandChristianity. TheBaltic godRugutis was worshiped as the agent of fermentation.Inalchemy, fermentation ("putrefaction") wassymbolizedbyCapricorn♑︎.
In 1837,Charles Cagniard de la Tour,Theodor SchwannandFriedrich Traugott Kützingindependently published papers concluding, as a result of microscopic investigations, that yeast is a living organism that reproduces bybudding.Schwann boiled grape juice to kill the yeast and found that no fermentation would occur until new yeast was added. However, a lot of chemists, includingAntoine Lavoisier, continued to view fermentation as a simple chemical reaction and rejected the notion that living organisms could be involved. This was seen as a reversion tovitalismand was lampooned in an anonymous publication byJustus von LiebigandFriedrich Wöhler.
The turning point came whenLouis Pasteur(1822–1895), during the 1850s and 1860s, repeated Schwann's experiments and showed fermentation is initiated by living organisms in a series of investigations.In 1857, Pasteur showed lactic acid fermentation is caused by living organisms.In 1860, he demonstrated how bacteria causesouringin milk, a process formerly thought to be merely a chemical change. His work in identifying the role of microorganisms in food spoilage led to the process ofpasteurization.
In 1877, working to improve the Frenchbrewing industry, Pasteur published his famous paper on fermentation, "Etudes sur la Bière", which was translated into English in 1879 as "Studies on fermentation".He defined fermentation (incorrectly) as "Life without air",yet he correctly showed how specific types of microorganisms cause specific types of fermentations and specific end-products.
Although showing fermentation resulted from the action of living microorganisms was a breakthrough, it did not explain the basic nature of fermentation; nor did it prove it is caused by microorganisms which appear to be always present. Many scientists, including Pasteur, had unsuccessfully attempted to extract the fermentation enzyme fromyeast.
Success came in 1897 when the German chemistEduard Buechnerground up yeast, extracted a juice from them, then found to his amazement this "dead" liquid would ferment a sugar solution, forming carbon dioxide and alcohol much like living yeasts.
Buechner's results are considered to mark the birth of biochemistry. The "unorganized ferments" behaved just like the organized ones. From that time on, the term enzyme came to be applied to all ferments. It was then understood fermentation is caused by enzymes produced by microorganisms.In 1907, Buechner won theNobel Prize in chemistryfor his work.
Advances in microbiology and fermentation technology have continued steadily up until the present. For example, in the 1930s, it was discovered microorganisms could bemutatedwith physical and chemical treatments to be higher-yielding, faster-growing, tolerant of less oxygen, and able to use a more concentrated medium.Strainselectionandhybridizationdeveloped as well, affecting most modern food fermentations.
The field of fermentation has been critical to producing a wide range of consumer goods, from food and drink to industrial chemicals and pharmaceuticals. Since its early beginnings in ancient civilizations, fermentation has continued to evolve and expand, with new techniques and technologies driving advances in product quality, yield, and efficiency. The period from the 1930s onward saw a number of significant advancements in fermentation technology, including the development of new processes for producing high-value products likeantibioticsandenzymes, the increasing importance of fermentation in the production of bulk chemicals, and a growing interest in the use of fermentation for the production offunctional foodsandnutraceuticals.
The 1950s and 1960s saw the development of new fermentation technologies, such as immobilized cells and enzymes, which allowed for more precise control over fermentation processes and increased the production of high-value products like antibiotics and enzymes. In the 1970s and 1980s, fermentation became increasingly important in producing bulk chemicals likeethanol,lactic acid, andcitric acid. This led to developing new fermentation techniques and genetically engineered microorganisms to improve yields and reduce production costs. In the 1990s and 2000s, there was a growing interest in fermentation to produce functional foods and nutraceuticals, which have potential health benefits beyond basic nutrition. This led to new fermentation processes,probiotics, and other functional ingredients.
Overall, the period from 1930 onward saw significant advancements in the use of fermentation for industrial purposes, leading to the production of a wide range of fermented products that are now consumed worldwide.