Services

• Fermentation CDMO Service
• Fermentation Process Optimization
• Strain Development Service
• GRAS Services
• Capabilities & Facilities
• Fermentation in Pharmaceuticals
• Fermentation for Special Small Molecules
• Fermentation in Human Nutrition
• Fermentation in Animal Health
• Fermentation Products
• Fermentation in Agriculture
• Fermentation in Industry
• GMP
• Environment, Health & Safety
• Microbial Metabolomics

BOC Sciences is a leading contract development and manufacturing company. We provide services for strain development, metabolic pathway engineering, strain improvement, protein expression, enzyme engineering and fermentation process development.

As a company specialized in microbial fermentation and precision fermentation, we fulfill projects tailored to your needs and help to improve manufacturability and process economy with any development stage and expression platform. We have FDA-approved GMP production sites, and we can provide one-stop services from concept to manufacturing. We focus on fermentation-related projects, providing high-quality fermentation services and fermentation products to meet the needs of customers in industries including pharmaceutical, food, agriculture and many others.

What is microbial fermentation?

The term "fermentation" refers to the process by which aerobic or anaerobic bacteria produce meals, drinks, or other valuable metabolites through the process of enzymatic conversions of substrates and regulated microbial growth. One of the fundamental aspects of natural microbial activities is metabolism, which enables the development and reproduction of bacteria. Fermentation is a process that occurs as a result of the natural activities of microbes. The destruction of substrates, as well as the development, reproduction, aging, and death of bacteria, are all components of the metabolic process. Additionally, the creation and modification of many metabolites are essential components of this process. First, microorganisms normally create signals in order to trigger the creation of proteins (enzymes) by detecting their surroundings. These proteins are then exported from the cell through a number of transport processes using the signals that they have produced. Enzymes are responsible for the conversion of substrates into the nutrients that are necessary for the development of the microbe. These nutrients include amino acids, nucleotides, sugar, fatty acids, and vitamins. Both the number of microbes and the accumulation of metabolic products lead to the initiation of novel metabolic pathways and the production of secondary metabolites. These secondary metabolites include pigments, antibiotics, poisons, and hormones. Microorganisms eventually start to perish as a result of the environment changing beyond the point where they are able to adapt to the new conditions. Microbial growth curves are often measured by workers in the laboratory. These curves are a representation of the dynamic population changes that occur when bacteria grow and divide in new and appropriate settings until they eventually die. Fermentation is a complicated process; microorganisms have very powerful regulatory systems, and even minute changes in the environment can result in the synthesis of a variety of diverse compounds.

Following the successful implementation of large-scale manufacturing and the discovery of penicillin, the laboratory decided to use the extremely effective culture flask ventilation and air fiber filtration sterilizing technologies. In addition to facilitating the application of microbial technology to the pharmaceutical business, the emergence of the antibiotic industry has also been a driving force behind the development of the aerobic industrial microbial fermentation sector. The focus of microbial engineering has shifted from decomposing metabolisms to synthesizing metabolisms in recent years. The accumulation of beneficial metabolic products, such as organic acids, enzyme preparations, vitamins, and hormones, that are outside of the typical metabolic spectrum of bacteria can be accomplished by the process of microbial synthesis of these substances. On account of this, the second significant turning point in the development of microbial engineering fermentation technology was the establishment of aerobic fermentation engineering technology for aerated stirring cultures.

The connection between fermentation and human existence. (Feng R., et al., 2018)

Microbial fermentation process

There are a number of essential phases involved in the process of microbial fermentation, which enables the transformation of substrates into useful products through the utilization of microorganisms.

• Microbe Selection: It is of the utmost importance to select the suitable microbe, as various microorganisms possess varying capacities and levels of productivity. In this case, the option is determined by the final product that is sought (for example, alcohol, acids, enzymes, or antibiotics).
• The preparation of the medium: development of microorganisms necessitates the presence of particular nutrients, which are supplied by the growth medium. These nutrients include carbon sources, such as sugars (glucose, sucrose), for the production of energy, and nitrogen sources, such as ammonia, nitrate, or organic nitrogen, for the production of proteins. These are the vitamins and minerals that are necessary for the proper functioning of enzymes and cells.
• Inoculum Preparation: In order to attain a suitable population size, an inoculum, also known as a starting culture, of the selected microbe is planted and grown under controlled circumstances. In order to do this, the microorganisms are grown in a little batch of media until they reach the concentration that is wanted.
• Batch, fed-batch, or continuous fermentation are the three modes that may be utilized to carry out the real fermentation process. Fermentation in batches involves the microbes, substrate, and nutrients being combined in a fermenter at the beginning of the process. The process continues without any further ingredients being added until it is finished. Through the use of fed-batch fermentation, new nutrients are introduced to the fermentation process on a regular basis in order to keep the growth conditions at their ideal level without diluting the culture to an excessive degree. A constant state of operation is maintained by continuous fermentation, which involves the addition of substrates on a continual basis and the removal of products on a continuous basis.
• During the fermentation process, it is essential to exercise strict control over many factors, including temperature, pH, oxygen supply (for aerobic processes), and agitation, in order to achieve the optimal environment for the process of microbial activity and product creation.
• The intended product must be retrieved from a combination of cells, unused substrates, and metabolic wastes in order to complete the process of product recovery, which occurs after fermentation. Centrifugation and filtration are two of the ways that are utilized in order to remove the microbial cells from the liquid. After the residual solution has been removed, the product is obtained. The nature of the product will determine whether or not this process involves crystallization, distillation, or any of the many other types of chromatography.

Common products of microbial fermentation

Microbial fermentation is a versatile process used across various industries to produce a wide array of products. These products can be broadly categorized into several groups based on their application and nature.

Food and Beverages: drinks, wines, and spirits are all made from ethanol, which is created by the fermentation of carbohydrates by yeasts, most often Saccharomyces cerevisiae. Alcoholic drinks are also known as alcoholic beverages. Among the dairy products, lactic acid bacteria (LAB) like Lactobacillus and Streptococcus are utilized in the manufacturing process of yogurt, cheese, kefir, and other fermented dairy products; Yeast fermentation results in the production of carbon dioxide and ethanol, which both contribute to the rise of bread dough and the development of its texture and flavor.

Organic raw material: The culinary, pharmaceutical, and cosmetic sectors all make extensive use of organic acids, including citric acid, lactic acid, and acetic acid, amongst others. For instance, the fungus Aspergillus niger is utilized in the production of citric acid.

Pharmaceuticals: The fermentation of particular molds or bacteria results in the production of a number of different antibiotics, including penicillin and streptomycin, among many others. Particular vitamins, such as vitamin B12 and riboflavin, are manufactured in a commercial setting by the process of microbial fermentation. Insulin, which was traditionally obtained from animals, is now widely generated by genetically engineered bacteria or yeast through the process of fermentation. Other medicinal proteins and enzymes are now created in a similar manner.

The applications of microbial fermentation. (Graham A E., et al., 2023)

Microbial fermentation technology

There are several different types of bioreactors, including the following: (1) Bench Scale Petri dish Erlenmeyer flask; (2) Tray Bioreactor; (3) Packed-bed Bioreactor; (4) Zymotis Bioreactor; (5) Rotating-drum Bioreactor; (6) Fluidized-bed Bioreactor; and (7) Spouted-bed Bioreacto.

Solid state fermentation, also known as SSF, is a technology of fermentation that is utilized by several sectors, including the pharmaceutical, textile, and food industries, among others, in order to generate metabolite bacteria by using solid support as an alternative to liquid medium utilization.

Submerged fermentation, also known as SmF, is a technique that involves the cultivation of microorganisms in a liquid broth medium. This medium is supplemented with essential nutrients in order to achieve a more effective cultivation of microorganisms. The process involves the cultivation of the selected microorganisms in closed reactors along with medium fermentation and a high concentration of oxygen.

Large-scale fermentation process. (Du Y H., et al., 2022)

Our fermentation services

Fermentation CDMO

As a contract development and manufacturing organization (CDMO), BOC Sciences provides world-class fermentation capabilities. We have fully controlled facilities for fermentation and downstream processing, and have extensive expertise and successful experience in the use of various vector development and large-scale production.

Strain Development

Using mutagenesis, gene recombination, high-throughput screening and genetic engineering directed breeding, we have been successfully developed/improved a variety of strains for our customers and help them transform primitive strains into industrializable strains.

Fermentation for Special Small Molecules

With more than 20 years of experience in the aspect of traditional strain technology, we can effectively find out the most functional strains combination to get the target small molecules. We can also optimize specific strain on current expression conditions, leading to higher protein expression in subsequent fermentation, increasing the yield of small molecules, and helping our clients discover possibility of the commercial production.

Fermentation Process Optimization

We have extensive expertise in scaling up and process optimization. Our dedicated facilities and processing capabilities for fermentation can support your biotechnology projects from inception to commercial scale.

We also provide strain development services and downstream process optimization and solutions for mature fermentation products to our industrial customers in various fields.

After obtaining the optimal strain, we optimize the fermentation process by tuning temperature, pH, dissolved oxygen and others to help find out the optimum combination of fermentation parameters covering upstream fermentation to downstream process.

We are committed to addressing your major concerns with solutions and are dedicated to maximize yields while maintaining the highest quality of products.

GRAS Services

GRAS is an FDA designation that experts believe the substances added to food are safe. An ingredient with a GRAS designation is exempted from the usual Federal Food, Drug, and Cosmetic Act (FFDCA) food additive tolerance requirements.

Our regulatory and scientific experts can help our clients complete GRAS evaluations, prepare the GRAS documentation to support the GRAS status of the ingredients.

Fermentation Capacity

Our state-of-the-art facilities have been FDA certified, with a fermentation capability exceeding 2,000,000 liters. We offer comprehensive services in upstream and downstream processes, quality control, regulatory compliance, and laboratory testing.

Our workforce comprises over 200 skilled and proficient professionals, and our R&D center spans an area of 2,200 square meters. We operate from 4 production bases, with specialized product lines for the pharmaceutical, food, and cosmetic industries.

We have 40+ reactors from 30 L to 4000 L, 170+ reactors from 20 KL to 30 KL, 24+ reactors with capacities exceeding 100 KL, as well as 2 hydrogenation reactors.

References

1. Feng R., et al., Fermentation trip: amazing microbes, amazing metabolisms, Annals of microbiology, 2018, 68: 717-729.
2. Microbial technology: Fermentation technology, Academic press, 2014.
3. Graham A E., et al., The microbial food revolution, Nature Communications, 2023, 14(1): 2231.
4. Hewitt C J., et al., The scale-up of microbial batch and fed-batch fermentation processes, Advances in applied microbiology, 2007, 62: 105-135.
5. Du Y H., et al., Optimization and scale-up of fermentation processes driven by models, Bioengineering, 2022, 9(9): 473.
6. Sun W., et al., Research progress of fermented functional foods and protein factory-microbial fermentation technology, Fermentation, 2022, 8(12): 688.