Fermentation

Fermentation is a natural process in which microorganisms like yeast and bacteria convert carbohydrates, such as starch and sugar, into alcohol or acids. The alcohol or acids generated then act as a natural preservative. In the case of fermented foods, this process gives the food a distinct zest and tartness, while also promoting the growth of beneficial bacteria. Also known as probiotics, these beneficial bacteria have been shown to improve immune function, digestive health, and heart health. Fermentation can also neutralize phytic acid, which causes mineral deficiencies and is found in grains, nuts, seeds, and legumes and makes starch, proteins, and fats less digestible.

Fermentation is used in the food industry for the production for alcoholic beverages, such as wine or vodka. It is used in bread making when yeast is combined with sugar, which it breaks down and gives off carbon dioxide to cause the bread to rise. And it is used to flavor and preserve dairy products or vegetables and to generate vinegars. The process of fermentation is also used in pharmaceuticals and therapeutics, in order to cultivate microorganism and material for antibiotics, therapeutic proteins, enzymes, and insulin. Fermentation has also been used to generate ethanol for the production of biofuel, and has been shown to be capable of producing hydrogen gas.

The process of fermentation in the manufacturing of beer or wine is a process that is estimated to be at least 10,000 years old. The frothing in these processes results from the evolution of carbon dioxide gas, which was not recognized until the 17th century. It was not until the 19th century when French chemist and microbiologist Louis Pasteur used fermentation in a narrow sense to describe the changes brought about by yeasts and other microorganisms in the absence of air. Pasteur was able to demonstrate that yeast is responsible for the transformation of glucose to ethanol in fermented beverages; he also discovered that microorganisms that cause milk to sour are from the action of bacteria in lactic acid fermentation.

There is evidence for fermentation as a natural practice in food for better holding qualities as far back as 10,000 BCE, with the milk of camels, goats, sheep, and cattle being naturally fermented. It is likely the fermentation occurred spontaneously in the subtropical climate, which also likely played a large role in the fermentation process. There has been some evidence to suggest that the first yogurts were produced in goat bags draped over the backs of camels in the heat of North Africa where high temperatures created the ideal conditions for fermentation.

The impact of fermented foods on human health was likely not well understood until 1910, when a Russian bacteriologist, Elie Metchnikoff, noted that Bulgarians had an average lifespan of 87 years, which was exceptional for the early 1900s. This led Metchnikoff to inspect the Bulgarian lifestyle to see what set them apart, and found they consumed a greater amount of fermented milks than other cultures. The bacteria found in these fermented milks was subsequently named Bulgarian Bacillus and would inspire a surge in the consumption of fermented milks with the perceived benefits of good health and longevity given to this strain of bacteria.

There are essentially three types of fermentation:

• Traditional fermentation causes change through microbial anaerobic digestion, which is used for developing products such as beer, wine, yogurt, and cheese, and is used to improve the flavor and functionality of ingredients.
• Biomass fermentation uses high-protein content and rapid growth of microorganisms to efficiently make large amounts of protein-rich food.
• Precision fermentation uses microorganisms to produce specific functional ingredients; it has been used to produce insulin or rennet.

The types of fermentation can be broken down further by the action taken from a biochemical view, which include anaerobic cellular respiration, fermentation, lactic acid fermentation, alcohol or ethanol fermentation, and facultative and obligate anaerobe fermentation.

Similar to aerobic cellular respiration, electrons are extracted from a fuel molecule and passed through an electron transport chain, which develops anaerobic cellular respiration and ATP synthesis. Some organisms use sulfate as a final electron acceptor on a transport chain, while others use nitrate, sulfur, or another variety of molecule. And prokaryotes, such as bacteria or archaea, use anaerobic respiration in low-oxygen environments to break down those fuels. For example, an archaea called methanogens can use carbon dioxide as a terminal electron acceptor and which produces methane as a byproduct. Methanogens can be found in soil and in the digestive systems of animals, such as cows and sheep, known as ruminants. Similarly, sulfate-reducing bacteria and archaea can use sulfate as a terminal electron acceptor and produces hydrogen sulfide as a byproduct.

Fermentation is an anaerobic pathway, or a pathway which does not require oxygen, for breaking down glucose performed by many types of organisms and cells. In fermentation, the only energy extraction pathway is glycolysis followed by an extra reaction or two at the end. In the process, the pyruvate made in glycolysis does not continue through the oxidation and citric acid cycles and the overall electron transport chain does not run. Because the electron transport chain is not functional, the NADH made in glycolysis cannot drop its electrons off and turn back into NAD+, and in fermentation the extra reactions are to regenerate the electron carrier NAD+ from the NADH produced in glycolysis. The extra reactions accomplish this by letting NADH drop the electrons off with an organic molecule, and this drop-off allows glycolysis to keep running with a steady supply of NAD+.

Lactic acid fermentation.

Lactic acid fermentation can be described as the metabolic process that transforms sugar into the metabolite lactate and energy. It is a respiration process that does not produce a gas and occurs in some bacteria. In lactic acid fermentation, NADH transfers its electrons to pyruvate and generates lactate as a byproduct. Lactate, which is the deprotonated form of lactic acid, gives name to the process. This process is used to process yogurt. It also occurs in red blood cells, which do not have the mitochondria to perform cellular respiration. Further, muscle cells carry out lactic acid fermentation when they have too little oxygen for aerobic respiration.

Alcohol and ethanol fermentation.

Alcohol fermentation is a process in which NADH donates its electrons to a derivate of pyruvate, which produces ethanol. This is a two-step process. The first step removes a carboxyl group from pyruvate and releases it as carbon dioxide, which produces a two-carbon molecule called acetaldehyde. In the second second step, NADH passes its electrons to acetaldehyde, regenerates NAD+ and forms ethanol. Alcohol fermentation by yeast produces the ethanol found in alcoholic drinks, such as beer or wine. Alcohol is toxic to yeasts in large quantities, which puts a limit on the percentage of alcohol in these drinks, with ethanol tolerance of yeast ranging from 5 to 21 percent depending on the yeast strain and environmental conditions.

Many bacteria and archaea are facultative anaerobes, which means they can switch between aerobic respiration and anaerobic pathways, such as fermentation and anaerobic respiration, based on the availability of oxygen. Other bacteria and archaea have been found to be obligate anaerobes, meaning they can only live and grow in the absence of oxygen exposure—meaning a normal atmospheric level of oxygen is toxic to these microorganisms. For instance, the Clostridium bacteria, which are responsible for botulism, are obligate anaerobes. As well, some multicellular animals have been discovered in deep-sea sediments that are anaerobic. These microorganisms get ATP out of their glucose molecules when oxygen is around to keep metabolizing in order to stay alive when oxygen is scarce.

In the process of fermentation, there is a need for a substrate, even if that substrate is mineral salts, light, and carbon dioxide, or if it is sugar, which can be provided at the beginning of the fermentation process or can be added over time. The choice of the different methods for performing fermentation can depend on the organism, application, and the final goal. These different methods could be summarized as batch processes, fed-batch processes, continuous culture, and open fermentation.

The batch process has all of the nutrients provided at the beginning of the cultivation and nothing more is added during the subsequent bioprocess. This means nothing during the entire bioprocess is added and the entire process is done in a closed system with the bioprocessing lasting until the nutrients are consumed. This method is suited for rapid experiments such as strain characterization or the optimization of nutrient medium. The disadvantage of this method is that the biomass and product yields are limited. Since the system is closed, the carbon source and oxygen transfer will be limiting factors and the microorganisms will not be in the exponential growth phase for a long time. To increase the availability of dissolved oxygen rate, the oxygen transfer rate is increased through increasing a stirring speed, gas flow rate, and the proportion of oxygen in the gas mix, as well as increasing the overall pressure in the batch container.

At the end of the bioprocess, the biomass or medium is harvested and processed for the desired product. From the bioreactor point of view, the processes is interrupted repeatedly by cleaning and sterilization steps and the biomass is only produced in stages. Batch process also have an increased risk for substrate or product inhibition as well as low yields. However, the overall advantages of batch cultures are the short duration of the process, a lower chance of contamination as nothing is added once the process is started, batch material can be separated to maintain traceability, and the batch process is easier to manage. While the disadvantages can include shorter productive time, batches can be stored for downstream processing, and the product is often mixed with other nutrients, reagents, cell debris, and toxins through the process.

As the name suggests, this process is a partially open system in which nutrients are constantly supplied during cultivation so nutrients do not become a limiting factor in the cultivation process. This process allows for overall higher product quantities, and under the right growth conditions, this process allows microorganisms and cells to constantly double and follow an exponential growth curve. This is allowed by the feed rate being able to increase with the growth rate, rather than in a closed batch process in which the feed does not change once the cultivation process starts.

In the fed-batch process, the substrate is generally pumped from the supply bottle into the culture vessel, and the user can set the feed at any time to either follow a linear flow, an exponential flow, or a pulse flow based on what conditions are necessary for the desired product. This level of control and the range of control strategies it allows can be suited for specialized applications. However, it can also increase the processing time and can lead to inhibition of the fermentation process through an accumulation of toxic byproducts. This process also requires a user to have a more in-depth understanding of bioprocesses to avoid certain toxin buildups.

Due in part to the advantages of a fed-batch process, it is often used in all areas of biotechnological production, in particular the production of recombinant proteins and antibiotics. The overall advantages of this process include the ability to extend a culture's productive duration, can be used to switch genes on or off through a changing structure, and can be used for maximum productivity using different feed strategies. While the disadvantages of the process includes the possible build up of inhibitory agents and toxins, the nutrient feed provides a point of possible contamination, and the process can produce a high cell density number and product yield which can be difficult to deal with.

A continuous culture uses a process similar to fed-batch, except it works to maintain an equilibrium in respect to a particular component. This includes introducing fresh culture medium as it is removed. This process is suitable especially when an excess of nutrients would result in inhibition due to toxin buildup or excessive heating. Other advantages of the continuous culture method include reduced product inhibition and an improved space-time yield. Once the medium is removed, cells are harvested, and the inflow and outflow rates must be less than the doubling time of the microorganisms. In a continuous process, the space-time yield of the bioreactor can be further improved on compared to a fed-batch process. However, the long cultivation period also increases the risk of contamination and long-term changes in the cultures.

Moreover, continuous processes have been ideal tools for gaining a better understanding of the process, since parameters remain constant when the system is operating. There are three common types of continuous cultures:

• Chemostat, in which the rate of addition of a single growth-limiting substrate controls cell multiplication
• Turbidostat, which is an indirect measurement of cell numbers (turbidity or optical density) controls the addition and removal of a liquid; this process requires additional sensors driven by real-time feedback
• Perfusion, in which the type of continuous bioprocessing mode is based on either retaining the cells in the bioreactor or recycling the cells back to the bioreactor; fresh medium is provided and cell-free supernatant gets removed at the same time

The advantages of the continuous culture process include allowing maximum productivity; reduced handling, cleaning, and sterilization time; and a steady state for metabolic studies when elements sum to zero. Some of the disadvantages of this process include the difficulty in keeping a constant population density over prolonged periods, the products of the continuous process not being neatly separated into batches for traceability, and the increased risk of contamination and genetic changes.

As the name suggests, the open fermentation process takes place in a vessel that is open to the environment. This is one of the oldest methods of fermentation and has been used for brewing beers and ales for a long time. Open fermentation needs to take place in an appropriate environment, due to the nature of the culturing vessel being open. Open fermentation often takes place in specially constructed rooms with smooth, easily cleaned surfaces to minimize the risk of microbiological contamination and must have good air flow to remove carbon dioxide given off during the fermentation. These fermentation rooms were designed with good natural air extraction, which have since been replaced by sophisticated extraction and air conditioning systems, including cooling systems for low temperature fermentation and heating systems for higher temperature fermentation processes, or fermentation processes in cold environments.

While there are many disadvantages to open fermentation, including the difficulty in cleaning these vessels, the increased possibility of contamination of the batch, and the impact of the environment on the fermentation process. However, this process is considered advantageous in the brewing of specific types of beers, especially as the brewer has a chance to see the fermentation and gauge its process in an open vessel. The vessels tend to be broad and shallow, and the shape encourages the formation of esters, which are often desirable in specific beers—especially beers, such as weissbier, which feature a yeast fermentation character. As well, open fermentation allows for the easy collection of the thick foam of floating yeast, which tends to be healthy and unencumbered by dead cells and protein sediment.

Solid-state fermentation (SSF) is, by definition, a process of fermentation carried out in absence of, or near absence of free water, meaning it uses solid materials as substrates for further biotransformation. This is a relatively newer form of fermentation, which has gained attention as a potential environmentally friendly technology that offers a chance to obtain bioproducts of industrial interest.

Although less employed at an industrial level, SSF is considered to offer some advantages over traditional or submerged fermentations, such as higher yields and productivities, extended stability of products, lower production cost, lower protein breakdown (which can be important if an enzyme is the target product), lower contamination risk, lower energy requirement, lower energy costs for sterilization, lower fermentor volume, and lower (or absent) catabolite repression. However, drawbacks related to poor homogeneity and energy and mass transfer often appear in SSF, which hinders the process yield and the downstream of the produce bioproducts.

Despite the difficulties, successful processes have been reported on the production of a variety of bioproducts, such as hydrolytic enzymes, mostly carbohydrases for bioethanol production, and to a lesser extent, aromas, biosurfactants, biopesticides, bioplastics, organic acids, or phenolic compounds. While most research into SSF seems to be focused on the process development at small scale, with some challenges in SSF relating to upscaling the development of a consistent and continuous operation.

Despite that, solid-state fermentation offers a possibility to use in natura (or non pretreated) agricultural and industrial wastes or byproducts, including raw materials, which can increase the economic feasibility of solid-state fermentation, especially as raw material is a commonly reported major operational cost in enzyme production processes.

There has been a series of technologies and methods used to advance fermentation and increase the use-cases and the products that fermentation is capable of producing. These advancements have come in the food and pharmaceutical industries, in biotechnology, and in the production of biofuels.

The food and pharmaceutical industries have combined techniques, such as ultrasound, ohmic heating, moderate electric field (MEF), pulsed electric field (PEF), and high-pressure processing during the fermentation process. The application of these techniques has been used to improve the fermentation process and advance the possibility of mycotoxin degradation through the interaction of effects of fermentation and these technologies. Some studies into this have found that ultrasound, ohmic heating, MEF, PEF, and cold plasma have positive effects on fermentation and the process of mycotoxin detoxification.

Similarly, fermentation has caught the attention for its possibility of accelerating and expanding biotechnology applications and commercialization. Especially as many new processes in fermentation use less farmland, water, or energy to develop new products, and some of these products have improved functionality due to the fermentation process. Specifically, alternative milks have been developed using a fermentation process that has given the product an identical mouthfeel as a dairy product but without adding emulsifiers. Fermented cheese alternatives have also garnered interest as the fermentation allows the alternative cheese product to melt and move similarly to the dairy product.

Fermentation has also been used in the production of bacterial insecticides, with two approaches developed to simplify the production of Bacillus thuringiensis and to bypass the ill-defined kinetics of oxygen requirement in the endotoxin formation. The first technique attempted used a semi-solid type of fermentation in large rectangular trays, where the inocula spread on a semi-permeable autoclavable cellulose sheets are placed on the surface. The endotoxin yield is then harvested from these cellulose sheets, and the technique offered some promising results for endotoxin yield and potency. The second approach used static growth of an organism in shallow trays with liquid media and in the presence of high redox potential compounds in order to minimize anaerobiosis.

Fermentation has been used in the production of ethanol from corn for a while. But a research team at the Integrated Bioprocessing Research Laboratory at the University of Illinois has worked to improve the dry-grind process used to process ethanol from corn. In the dry-grind process, corn starch is converted into glucose which is fermented by yeast and produces ethanol. However, ethanol build up during the fermentation can inhibit the yeast, and the yeast can no longer efficiently convert sugar into alcohol. The typical dry-grind process takes place in a slurry, which mixes ground corn with water, and consists of 30 to 33 percent corn solids. However, the researchers were able to use up to 42 percent of corn solids. This was accomplished using an intermittent vacuum flashing process which removed ethanol from the fermentation tank and was able to stop the ethanol from building up to a concentration where it inhibited the yeast. This allowed for greater concentrations of ethanol to be acquired from the process and was also proven to be twice as fast as the conventional process.

One of the oldest uses for fermentation is the processing of food and alcohol to either increase its lifetime or to create novel food types. Common fermented foods have included the following:

• Kefir
• Sauerkraut
• Tempeh
• Cheese
• Kombucha
• Miso
• Kimchi
• Salami
• Pickles
• Yogurt
• Beer
• Wine

The fermentation process allows many foods to remain edible for longer periods of time and allows them to be stored without refrigeration. In some cases, fermentation also offers a process through which foods can be consumed safely. It took longer to understand the health benefits of fermented foods, with the first indication coming in the early 20th century and gaining better understanding since. Fermented foods offer a variety of health benefits:

• An improvement in digestive health: this is done through the probiotics produced during the fermentation process, which have been shown able to restore the balance of friendly bacteria in a gut and capable of alleviating some digestive problems.
• A boost to the immune system: fermented foods, by improving the bacteria in the gut microbiome, have been proven to have a positive impact on the immune system. The probiotic content of fermented foods can boost the immune system and help reduce the risk of infections. As well, these foods tend to be rich in vitamin C, iron, and zinc.
• Improvement in digestibility in some foods: the fermentation process breaks nutrients down before they enter the body, easing the burden of digestion compared to unfermented foods. For example, lactose, when broken down during fermentation into simpler sugars, such as glucose and galactose, can allow those with an intolerance to lactose eat fermented dairy with little to no problems.
• The potential of promoting mental health: according to some studies that link probiotic strains lactobacillus helveticus and bifidobacterium longum (both of which are found in fermented foods) to a reduction in symptoms of anxiety and depression.
• Potential to aid in weight loss, decreased belly fat, and a lower risk of heart disease and high blood pressure: according to studies that have linked certain probiotic strains found in fermented foods, including lactobacillus rhamnosus and lactobacillus gasseri.

Ingredients made with fermentation have been used for plant-based and cultivated products, which have led to plant-based, fermentation-derived, and cultivated products more of an intersection of food technology rather than indistinct categories. For plant-based meat, eggs, and dairy alternatives, the fermentation process has been shown to help digestibility, taste, texture, and nutrients of the ingredients of the final product. And proteins such as collagen or fibronectin, both of which can be produced through fermentation, have been suggested as important for animal-free components of scaffolding for more complex cultivated meat products. With the use of fermentation and various other techniques, this has allowed biotechnology company to create proteins that rival those found in animal products and which could challenge the industrial meat, egg, and dairy industries.

The alternative protein production through fermentation has also been considered by some to be more efficient than conventional protein or meat production, with fermentation offering advantages that can increase the efficiency of the alternative protein section. This includes minimizing food waste and transforming low-value agricultural side streams into nutritious food through fermentation. This has been tested using fermentation to improve the digestibility, taste, texture, and nutrients of pressed sunflower cakes.

Fermentation can produce stand-alone protein sources for plant-based and cultivated meat products, and it can act as a technology to provide ingredients for these products. In either way, the fermentation for alternative protein category can be segmented into two categories: biomass, which is used to create a large amount of protein; or synthetic biology, also known as recombinant protein technology, which can produce an individual functional protein.

In biomass, the bacteria are used to consume carbon dioxide and agricultural side streams, such as feedstock, in order to produce a protein ingredient. This could include things like mycoprotein, which is based on the fermentation of fungi in bioreactors, and has proven to be a great source material for meat analogue products.

This method of fermentation has been used in the cultivated meat space to move towards a commercial scale. As fermentation can be used to grow animal cells for the cultured meat industry, as the current technologies for doing so are considered almost prohibitively expensive.

However, both fermentation technologies have been used to produce ingredients intended to improve the performance of plant-based products. This includes tackling challenges such as getting plant proteins to be globular similar to animal proteins, and creating plant proteins that are fibular and cross-lined similar to animal proteins, which are responsible for the texture and mouthfeel associated with meat. This could also address some of the sensory challenges facing the plant-based meat industry and optimize flavor and functionality through additives.

Similar to the overall alternative industry protein market, fermentation offers a chance to create whole-muscle cut seafood analogues. This has been done through microbial fermentation process which is able of producing a complete protein, which has so far been used to develop shrimp, calamari, ahi tuna, generalized fish fillets, and popcorn shrimp products. The process used is biomass fermentation in order to create large groups of microorganisms as an ingredient for these alternative seafood products. This process has also used fungi-based products and was able to reduce or remove the need for starches and isolates often used in these products, and was able to develop a better nutrition profiles with fiber, micronutrients, and naturally-occurring proteins, while also providing the bite, texture, and sensorial experience similar to eating whole cuts of fish.

The use of mycoprotein fermentation of mycelium, which is the root structure of mushrooms, for plant-based protein has been more widespread, as it offers a texture similar to meat while requiring less processing than other methods. Further, it is naturally high in protein, iron, and fiber. One such product, known as Rhiza, has a neutral flavor, which allows companies to further flavor and balance the moisture and texture in order to imitate the desired food product.

Companies have begun to develop chocolate without the use of cocoa, removing what can be considered a controversial ingredient. One such company, QOA, has been able to do this using a precision fermentation method that recreates the composition of cocoa using other food materials. This process is similar to brewing beer, with QOA analyzing various food byproducts to find which ones can be combined to match the flavor profile of cocoa. An example of this is the leftover residue from the production of olive, grapeseed, or sunflower oil. Fermenting these ingredients gives what the company considers a ground for growing the building blocks to making a cocoa alternative. Once fermented, the ingredients can be roasted like a regular cocoa bean and included in chocolate to develop a product that is vegan, non-GMO, and gluten- and dairy-free.

Fermentation, as a process which can cultivate microorganisms or other organic material, has been used by the pharmaceutical and therapeutic industries in order to develop certain antibiotics, therapeutic proteins, enzymes, and insulin. Production typically carried out in temperature-controlled tanks, also known as fermenters or bioreactors, and allows users to use the correct concentration of nutrients in order to produce the organism of interest.

The molecules of interest in the pharmaceutical industry tend to be short peptides and low molecular weight organic molecules, larger molecules such as proteins or nucleic acids, and macromolecules such as lipids and carbohydrate polymers. Fermentation also offers a chance to create various combination product types, such as lipopolysaccharides, lipopeptides, peptidoglycan, all of which could potentially serve as a pharmaceutical's active ingredient.

Microbial fermentation has been used for the production of a range of pharmaceutical products. With 2009 having more than 150 recombinant pharmaceuticals produced and approved for human use by the FDA and the EMA, with more than half of those being manufactured through microbial fermentation using bacteria or yeast. This has since increased interest in microbial production with the overall market for microbial fermentation since expanding. Examples of some products developed with microbial fermentation or products from microbial fermentation include:

• Anticancer cytotoxic drugs and vaccines
• Anti-infectious disease antibiotics and vaccines
• Hormonal disorder therapy

In many cases, the high cost and long development timelines and lower expression levels associated with mammalian cell cultures have contributed to the resurgence of interest in manufacturing processes that use microbial fermentation. Especially as microbial fermentation has proven to be a better option for the production of complex drug substances, such as single-domain antibodies, peptibodies, and antibody fragments with the ability to create the right properties in clinically relevant amounts. Microbial fermentation has also provided faster development, higher yields and better quality, reduce variation between batches, and better scalability than other production methods, as well as offering lower production costs.

As well, the applications for microbial fermentation have expanded. These applications have drawn on the use of microbial biofactories to offer the pharmaceutical industry a source for therapeutic ingredients through isolated microbial fermentation:

These toxic, small, organic molecules produced by microorganisms developed in response to stress are called secondary metabolites. They have seen use in cancer therapy and the treatment of infectious disease. As well, many antibiotics have been sourced from living microorganisms used either in their natural state or in a chemically modified state. For example, aminoglycosides are produced and isolated from bacteria of the Streptomyces genus.

Fermentation-derived biological therapeutics have been used in a wide range of medical indications. This has included native proteins, such as collagenases, a group of enzymes produced by the bacterial pathogen Clostridium genus, and used in a variety of medical indications involving collagen disorders and the removal of dead skin from wounds and burn areas in poorly healing wounds and necrosis.

In the case of biofuel, the use of ethanol fermentation has been used, a process in which yeast and certain bacteria is broken into ethanol and carbon dioxide. This has been used in the production of beer, wine, and bread, but can also be used for the production of ethanol for biofuel. In the case of biofuel, the ethanol biofuel can be made from various plant materials, also known as biomass, which can then be used as a blending agent with gasoline to increase octane and reduce carbon monoxide and other smog-causing emissions.

Most ethanol for biofuels is made from plant starches and sugars, with more developments to allow for an increased use of cellulose and hemicellulose, the non-edible fibrous material which constitutes the bulk of plant matter.

As well, in the case of biofuels, fermentation can be used to upgrade crude bio-oils, syngas, sugars, and other chemical building blocks which need to be upgraded to produce a finished product. Often the fermented sugar or gaseous intermediates, which use bacteria, yeast, and cyanobacteria, can be processed in order to improve storage and handling properties.