Microbial metabolism

MICROBIAL METABOLISM

As in most other aspects of their physiology, microorganisms exhibit marked differences in their metabolism. While some species can obtain carbon from carbon dioxide and energy from sunlight or the oxidation of inorganic materials like sulphides, the vast majority of organisms of interest in pharmacy and medicine are described as chemoheterotrophs—they obtain carbon, nitrogen and energy by breaking down organic compounds. The chemical reactions by which energy is liberated by digestion of food materials are termed catabolic reactions, while those that use the liberated energy to make complex cellular polymers, proteins, carbohydrates and nucleic acids, are called anabolic reactions.

Food materials are oxidized in order to break them down and release energy from them. The term oxidation is defined as the removal or loss of electrons, but oxidation does not invariably involve oxygen, as a wide variety of other molecules can accept electrons and thus act as oxidizing agents. As the oxidizing molecule accepts the electrons, the other molecule in the reaction that provides them is simultaneously reduced. Consequently, oxidation and reduction are invariably linked and such reactions are often termed redox reactions. The term redox potential is also used, and this indicates whether oxidizing or reducing conditions prevail in a particular situation, e.g. in a body fluid or a culture medium. Anaerobic organisms prefer low redox potentials (typically zero to −200 mV or less) while aerobes thrive in high redox potential environments (e.g. zero to +200 mV or more).

There are marked similarities in the metabolic pathways used by pathogenic bacteria and by mammals. Many bacteria use the same process of glycolysis that is used by humans to begin the breakdown of glucose and the release of energy from it. Glycolysis describes the conversion of glucose, through a series of reactions, to pyruvic acid, and it is a process for which oxygen is not required, although glycolysis is undertaken by both aerobic and anaerobic organisms. The process releases only a relatively small amount of the energy stored in a sugar molecule, and aerobic microorganisms, in common with mammals, release much more of the energy by aerobic respiration. Oxygen is the molecule at the end of the sequence of respiratory reactions that finally accepts the electrons and allows the whole process to proceed, but it is worth noting that many organisms can also undertake anaerobic respiration, which uses other final electron acceptors, e.g. nitrate or fumarate.

As an alternative to respiration many microorganisms use fermentation as a means of releasing more energy from sugar; fermentation is, by definition, a process in which the final electron acceptor is an organic molecule. The term is widely understood to mean the production by yeast of ethanol and carbon dioxide from sugar, but in fact many organisms apart from yeasts can undertake fermentation and the process is not restricted to common sugar (sucrose) as a starting material or to ethanol and carbon dioxide as metabolic products. Many pathogenic bacteria are capable of fermenting several different sugars and other organic materials to give a range of metabolic products that includes acids (e.g. lactic, acetic and propionic), alcohols (e.g. ethanol, propanol, butanediol) and other commercially important materials like the solvents acetone and butanol. Fermentation is, like glycolysis, an anaerobic process, although the term is commonly used in the pharmaceutical and biotechnology industries to describe the manufacture of a wide range of substances by microorganisms where the biochemical process is neither fermentative nor even anaerobic, e.g. many textbooks refer to antibiotic fermentation, but the production vessels are usually vigorously aerated.

Microorganisms are far more versatile than mammals with respect to the materials that they can use as foods and the means by which those foods are broken down. Some pathogenic organisms can grow on dilute solutions of mineral salts and sugar (or other simple molecules like glycerol, lactic or pyruvic acids), while others can obtain energy from rarely encountered carbohydrates or by the digestion of proteins or other noncarbohydrate foods. In addition to accepting a wide variety of food materials, many microorganisms can use alternative metabolic pathways to break the food down depending on the environmental conditions, e.g. facultative anaerobes can switch from respiration to fermentation if oxygen supplies are depleted. It is partly this ability to switch to different metabolic pathways that explains why none of the major antibiotics work by interfering with the chemical reactions microorganisms use to metabolize their food. It is a fundamental principle of antibiotic action that the drug must exploit a difference in metabolism between the organism to be killed and the human host; without such a difference the antibiotic would be very toxic to the patient too. However, not only do bacteria use metabolic pathways for food digestion that are similar to our own, many of them would have the ability to switch to an alternative energy producing pathway if an antibiotic were developed that interfered with a reaction that is unique to bacteria.

The metabolic products that arise during the period when a microbial culture is actually growing are termed primary metabolites, while those that are produced after cell multiplication has slowed or stopped, i.e. in the ‘stationary phase’ , are termed secondary metabolites. Ethanol is a primary metabolite of major commercial importance although it is produced in large quantities only by some species of yeast. More common than ethanol as primary metabolites are organic acids, so it is a common observation that the pH of a culture progressively falls during growth, and many organisms further metabolize the acids so the pH often rises after cell growth has ceased. The metabolites that are found during secondary metabolism are diverse, and many of them have commercial or therapeutic importance. They include antibiotics, enzymes (e.g. amylases that digest starch and proteolytic enzymes used in biological washing powders), toxins (responsible for many of the symptoms of infection but some also of therapeutic values. e.g. botox—the toxin of Clostridium botulinum) and carbohydrates (e.g. dextran, used as a plasma expander and for molecular separations by gel filtration).