Fermentation in Microbial Metabolism

During the process of growth and metabolism, microorganisms secrete two types of metabolic products: primary metabolites and secondary metabolites. The former includes substances such as amino acids, nucleic acids, lipids, and carbohydrates, produced by microorganisms during the logarithmic growth phase. The latter includes products like antibiotics, alkaloids, and plant growth factors, synthesized by microorganisms during the stationary phase.

• Antibiotics
  
  The most important microbial product in industrial production is antibiotics. Antibiotics are chemical substances produced by microorganisms that can kill or inhibit the growth of other microorganisms. They have significant impact and application in the field of medicine. Antibiotics are secondary metabolites. Although their production yield is relatively low in most industrial fermentations, they have high therapeutic efficacy and industrial value, making them suitable for large-scale production using microbial fermentation. While many vitamins can be chemically synthesized, antibiotics have complex chemical structures and their chemical synthesis is costly, making them less likely to be produced through chemical methods.
  The economically valuable antibiotics are mainly produced by Actinomyces, a genus of filamentous bacteria, and some are produced by fungal species.
  
  
• Vitamins
  
  Vitamins are essential as food and feed additives and are commercially produced through chemical synthesis. However, the synthesis of certain vitamins involves complex techniques that make it difficult to achieve low-cost production. In such cases, microbial fermentation methods are employed. Vitamin B12, for example, is currently industrially produced through fermentation. Certain strains of Propionibacterium, a genus of bacteria, are selected and used for vitamin production, with a yield of 1923 mg/L. The presence of cobalt in the culture medium significantly enhances the production of vitamin B12, as it is an essential component of its structure. Riboflavin is a precursor to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), both of which play important roles as coenzymes in the oxidative-reduction enzyme systems of all living organisms. Various microorganisms, including bacteria, yeast, and fungi, can synthesize riboflavin. Aspergillus niger, a filamentous fungus, is capable of producing significant amounts of riboflavin during its growth process.
  
  
• Amino Acids
  
  Amino acids find extensive applications as food additives in the food industry, in the medical field, and as raw materials in the chemical industry. Glutamic acid, in particular, is an important flavor enhancer. Two other significant amino acids, aspartic acid and phenylalanine, are components of the artificial sweetener L-aspartyl-L-phenylalanine methyl ester, which is used in the production of sugar-free soft drinks and other food products. While most amino acids can be synthesized chemically, the resulting products are often a mixture of D and L stereoisomers. To obtain specific chiral amino acids with biological significance, acid-promoted reactions or microbial methods are required. Various organisms produce a wide range of enzymes, most of which are involved in cellular processes in small amounts. However, some organisms can produce large quantities of specific enzymes, which are secreted into the culture medium. These extracellular enzymes usually act on soluble nutrients, such as cellulose, proteins, and starch, digesting them into products that can serve as nutrients for bacterial growth. Some extracellular enzymes are used in food processing and textile industries and can be synthesized and produced in large quantities by microorganisms.
  
  Enzymes for industrial production can be produced by bacteria and fungi. The production process is usually aerobic, and the culture medium is similar to that used for antibiotic fermentation. Induction of enzymes can be achieved by adding appropriate inducers to the culture medium.
  
  
• Citric Acid and Other Organic Compounds
  
  Many organic compounds are produced through industrial fermentation by high-yield microorganisms. Citric acid is widely used in the food and beverage industry, itaconic acid is used in the production of acrylic acid resins, and gluconic acid, produced by fungi, is used in the production of calcium gluconate, which serves as a calcium supplement and is used as a detergent and softener in the industry. Sorbitol is produced during the oxidation of sorbitol by acetic acid bacteria and is used in the production of ascorbic acid (vitamin C). Gibberellins, produced by fungi, are plant growth hormones used to stimulate plant growth. Dextran is a gum used in the production of plasma expanders and biochemical reagents. Lactic acid, produced by lactobacilli, is used for acidification in the food industry and beverages.
  
  

Characteristics and Trends in Fermentation Industry

1.Characteristics of the Fermentation Industry

The fermentation industry utilizes the chemical activity of microorganisms to carry out substance transformation, and the industrial production using this process is called the fermentation industry. The fermentation industry has unique advantages, which have led to a shift from chemical synthesis to fermentation production for many products. The advantages of the fermentation industry are as follows:

1. Microbial reactions are usually conducted at room temperature, while chemical synthesis often requires high-pressure reactions that involve higher operational risks.
   
   
2. Microbial reactors are mostly aerobic, agitated, and versatile. The same type or similar reactors can produce various products. For example, a production line in a pharmaceutical factory can produce three different antibiotics.
   
   
3. The raw materials used in production are primarily agricultural by-products, which are suitable for China's national conditions. For example, in the fermentation of citric acid, China uses dried sweet potatoes as raw materials, which gives the product a competitive edge in the international market.
   
   
4. Fermentation industry exhibits a high degree of selectivity, which is achieved through the specific stress response mechanisms of microorganisms. For example, yellow short rod bacteria can convert shikimic acid into L-apple acid, while chemical synthesis can only yield DL-apple acid.
   
   
5. Through strain breeding techniques such as mutation breeding and hybrid breeding, as well as genetic engineering, production efficiency can be significantly improved. For example, in penicillin production, the initial fermentation units had only 2 units/mL, but now it has reached 85,000 units/mL, with a significant contribution from strain breeding.
   
   
6. Certain modern bioproducts, such as enzymes, B vaccines, and growth factors, can only be produced through fermentation using genetically engineered microorganisms or cells.

Despite the advantages of the fermentation industry, it also has some drawbacks:

1. It consumes a large amount of energy, especially equipment such as air compressors and agitators, which consume significant amounts of energy. The microorganisms in the fermentation vessel require continuous oxygen supply and agitation, and a long cessation of oxygen supply and agitation can result in microbial inactivation and product loss.
   
   
2. The fermentation industry relies on the growth and metabolism of microorganisms to produce products, which leads to the consumption of large amounts of raw materials for microbial growth. However, the microorganisms themselves are useless and can sometimes cause environmental pollution.
   
   
3. The solvent in microbial reactions is primarily water, which results in high substrate concentrations in the culture medium. This requires the use of large-volume fermentation vessels, but the product yield is relatively low, resulting in lower efficiency.
   
   
4. During product collection in fermentation, after a small amount of product is harvested, the remaining liquid needs to be treated or recycled. Additionally, the water used for fermentation washes is substantial, and the wastewater usually has a high biochemical oxygen demand (BOD), causing pollution.

Due to the aforementioned disadvantages of the fermentation industry and the development of the petrochemical industry, which provides abundant and inexpensive raw materials for chemical synthesis, the competition between microbial fermentation technology and chemical synthesis engineering is intense. In some cases, the production techniques that combine the advantages of both approaches have achieved better economic benefits. For example, the production of vitamin C involves using microbial fermentation to convert sorbitol to sorbose, which is then chemically synthesized into vitamin C.

2. Current Status and Trends of the Fermentation Industry

Among countries worldwide, the United States has the largest scale and highest production value in the fermentation industry. Currently, over 100 types of products are produced on a large scale. The fermentation industry in Japan has experienced rapid development in the past 20 years, particularly in areas such as amino acid fermentation, nucleic acid fermentation, and immobilized cell production of organic acids, where it holds a leading position.