Biosynthetics
Biosynthetics refer to materials produced through biosynthetic processes that utilize small, simple molecules to create larger, complex ones, often inside living organisms or in laboratory settings. This process is fundamental in various fields, including medicine, where it enables the synthesis of proteins, hormones, dietary supplements, and surgical dressings. By employing enzymes and energetic molecules, biosynthetic pathways can produce primary metabolites necessary for cell function, as well as secondary metabolites like antibiotics and vitamins that support overall health.
Historically, the field was pioneered by scientists such as Hermann Karl Felix Blaschko, who laid the groundwork for understanding biochemical pathways in the 1930s. Over the decades, advancements have led to practical applications like therapeutic proteins, biosensors, and innovative drug delivery systems. Additionally, the textile industry is exploring biosynthetic fabrics derived from plant materials, which could reduce reliance on fossil fuel-based synthetics.
As biosynthetic research continues to evolve, it addresses growing healthcare needs and ethical considerations surrounding the use of biosynthetic products, especially in nonmedical settings like bodybuilding. With an increasing global population and aging demographic, the significance of biosynthetics is expected to rise, offering potential solutions for a wide range of health and sustainability challenges.
Biosynthetics
Summary
Biosynthesis is the process of using small, simple molecules to make larger, more complex molecules, either inside the body or in the laboratory. Numerous drug development and medicine applications include synthesizing proteins, hormones, dietary supplements, blood products, and surgical dressings for wounds. Additional techniques to facilitate the diagnosis and treatment of disease include protein biomarkers for immune assays, the development of proteomics to analyze changes in proteins in response to a drug, the development of polyclonal and monoclonal antibodies, immunizations, and various drug delivery systems. The textile and fashion industries are also involved in developing biosynthetic products.
Definition and Basic Principles
The term biosynthetic refers to any material produced via a biosynthetic process. A biosynthetic process uses enzymes and energetic molecules to transform small molecules into larger molecules within the cells of organisms. The two metabolites produced from cellular biosynthetic pathways include the primary metabolites of fatty acids and DNA needed by cells and the secondary metabolites of pheromones, antibiotics, and vitamins that assist the entire organism. Additional small molecules, such as adenosine triphosphate (ATP), provide the energetic driving force for the biosynthetic pathways, and other small molecules, including enzymes, further facilitate the reactions in these pathways. Thus, there have been many possibilities for numerous scientists, including chemists, biochemists, biologists, and geneticists, to create innovations.
Biosynthetic differs from the term chemosynthetic because chemosynthetic indicates the production of materials that cannot occur within a living organism. Scientists begin developing a new medical application or dietary supplement by first isolating and characterizing the DNA of the proteins or other small molecules directly involved in the biological process. They try to duplicate this naturally occurring biological process to produce massive quantities of the desired material and ultimately combine these naturally occurring processes with chemicals that mimic the process during laboratory manufacturing processes.
Background and History
The biochemical pharmacologist Hermann Karl Felix “Hugh” Blaschko was a trailblazer whose discoveries in the 1930s initiated the field of biosynthetics. His work elucidated the biosynthetic pathway for adrenaline, often called the fight-and-flight hormone, and encompassed the study of the enzymes important for regulating this hormone. This work led the way toward developing syntheses using amino acids for therapeutic applications.
Another key development was the discovery of the role of the amino acid L-arginine in the synthesis of creatine, an important biomolecule, by G. L. Foster, Rudolf Schoenheimer, and D. Rittenberg in 1939. Since then, L-arginine has been shown to be a precursor to nitrous oxide and nitric oxide, as well as a component of the urea cycle, which is important for ammonia regulation and thus influences the operation of the kidneys and other organs. Nitric oxide is important in the regulation of blood flow to muscles. These discoveries involving L-arginine have led to dietary supplements used by bodybuilders to enhance their weight-lifting performance.
Throughout the 1940s, 1950s, and 1960s, progress was made toward understanding the genetic composition of organisms, enzymes, and biosynthetic pathways. Researchers made contributions to understanding pyrimidine, galactosidase, Escherichia coli, and chlorophyll. Practical biosynthetic applications made possible by these fundamental discoveries began to manifest themselves throughout the 1970s, 1980s, and 1990s, with the development of surgical dressings, therapeutic hormones, and plant supplements for increased nutritional value.
How It Works
General Process. Often the isolation and characterization of a specific gene responsible for producing an important enzyme or other small molecule is the first step in a lengthy process toward synthesis of a product that undergoes lengthy clinical trials before the final, approved product is ready for manufacture. Once the gene has been characterized, its DNA is further characterized to facilitate the process of peptide synthesis (the process of producing long peptides is known as protein biosynthesis).
The process of peptide synthesis involves the general concepts of antigenicity, hydrophilicity, surface probability, and flexibility indexes. The process involves an analysis of the peptide's characteristics, the use of software and databases to determine hydrophilicity (affinity for water), the study of the antigenicity (capacity to stimulate the production of antibodies) to assist with antibody production, the study of surface probability (which determines the likelihood of inducing the formation of antibodies), the determination of the protein sequence, phosphorylation (process that activates or deactivates many protein enzymes), and then selection of two to three peptides, followed by comparison of their homology (similarity of structure).
In a general process called screening, the efficacy of an antibiotic is first tested using bacterial cultures, followed by injection of the antibiotic into laboratory animals, such as rats, rabbits, or guinea pigs. Then clinical trials are conducted according to protocols established by the Food and Drug Administration (FDA). Combinatorial chemistry, a faster screening method, is often used instead. FDA-approved products are then manufactured on a larger scale.
Antibody Production. A binding assay is used to isolate the purified protein that is the source of an antigen. This antigen is used as a conjugate to a carrier protein, such as keyhole limpet hemocyanin (KLH), to produce a target peptide with a length of thirteen to twenty amino acids to stimulate the immune system. A carrier protein is a membrane protein that can bind to a substance to facilitate the substance's passive transport into a cell. Injection into a laboratory animal occurs next, and then the animals undergo a series of four to six immunizations separated by about twenty days. Enzyme-linked immunosorbent assay (ELISA) is used to detect antibodies. ELISA is based on the antibody-antigen binding interaction and often uses color to visually indicate the concentration of antibodies. Purification of antibodies obtained from the antiserum for specific antigen binding completes the antibody production process.
Antigen Preparation. This process is facilitated through bioinformatics analysis to choose the appropriate two to three peptides based on the protein sequence provided by a customer. KLH conjugation is used for immunization, and bovine serum albumin (BSA) conjugation is carried out for screening. After immunization protocols and specific antibodies have been selected during fusion and screening, a cell can be cryopreserved.
Combinatorial Chemistry. In combinatorial chemistry synthesis, a high-throughput screening method, the starting small molecule is attached to a type of polymeric resin, followed by different permutations of reagents, to produce large libraries containing hundreds of unique products that can be rapidly screened for enzymatic activity, specific antigen-binding, or protein-protein interactions. Often the process is controlled by a computer and completed using robotics. A customer can specify antigen details, and a pharmaceutical company can design a protocol involving the general phases of preparation of antigen, immunization, fusion and screening of assays, and finally selection, purification, and production of antibodies.
Applications and Products
Biosensors.Biosensors are microelectronic devices that use antibodies, enzymes, or other biological molecules to interact with an optical device or electrode to record data electronically. These devices can be operated by home health care providers to transmit data obtained from blood or urine samples, for example, to a clinical laboratory some distance away.
Therapeutic Proteins.Plasmids are used to transfer human genes that provide the code for proteins important for growth hormones, blood clotting, and insulin production to bacterial cells.
Disposable Micropumps for Drug Delivery. Disposable micropumps manufactured by Acuros in Germany can deliver a preset amount of liquid hormones, proteins, antibodies, or other medications. An osmotic microactuator, based on osmotic pressure, is used to regulate the amount of drug delivered, and there are no moving parts or power supply components.
High-Throughput Screening. High-throughput screening can assay more than twenty thousand potentially useful drugs per week using multiwell plates, standard binding assay methodologies, and robotics.
Protein Biomarker Assays. NextGen Sciences has developed a mass spectrometry method for protein biomarker assays that does not depend on antibodies but instead uses surrogate proteins to facilitate the development of assays. The mass spectrometer measures the amount of surrogate peptides and applies statistical evaluation to assess each biomarker. This first stage requires the confirmation of a protein. Then, only these selected proteins are used for the second stage of validating these protein biomarkers. The mass spectrometry data are used along with carbon-13 or nitrogen-15 isotopically labeled standards to calculate protein concentrations. Reporting the protein biomarkers in terms of concentration is important to allow batches containing hundreds of samples to be analyzed and validated. This technique uses proteomics (the quantitative analysis of proteins based on a physiological response) to allow for much faster development of assays than immunoassays. A wide range of at least 500 plasma and 3,000 tissue proteins can be analyzed at one time.
Gene Expression Databases. Gene Logic's BioExpress System is a comprehensive genome-wide gene expression database. The BioExpress System allows cells from a patient to be collected and analyzed to develop a useful biomarker profile for comparison with a database sample to indicate a therapeutic target. This process is possible using high-throughput gene expression profiling of the mononuclear cell fractions in a blood sample. The software is capable of mining a database that has access to more than 18,000 samples containing biomarkers for the expression of the gene associated with ovarian cancer. This system can develop biomarker profiles to help diagnose autoimmune diseases. Autoimmune diseases include rheumatoid arthritis, Crohn's disease, multiple sclerosis, systemic lupus erythematosus, and psoriasis, which affect about 20 million people in the United States.
Biosynthetic Temporary Skin Substitute. A biosynthetic skin substitute is useful for partial-thickness wounds, including skin tears, burns, and abrasions. After applying a gel to the wound’s surface, a semipermeable membrane of biosynthetic skin is used to cover the wound for protection from infection. Before the development of biosynthetic skin grafts, a physician had to choose between an allograft, which uses cadaver skin, and a xenograft, which uses tissue from another species. Biosynthetic dressings have also been developed. The dressing called Hydrofiber contains ionic silver and has been shown to prevent the spread of bacteria.
Needle-Free Drug Delivery Systems. The three types of needle-free drug delivery systems are liquid, powder, and depot injections. Each uses some form of mechanical compression to create enough pressure to force the medication into the skin. Although these needle-free delivery systems cost more initially and require more technical expertise because of their complexity, they also have many advantages. In addition to eliminating pain from needle injections and reducing physician visits, these needle-free delivery systems decrease the frequency of incorrect doses. They are used to deliver anesthetics, chemotherapy injections, vaccines, and hormones.
Nanoparticles. DNA nanotechnology uses discoveries involving nanoparticles and nanomaterials to manipulate DNA's molecular recognition abilities to build tiny medical robots that mimic bond parts or function within cells.
Sustainable Textiles. Biosynthetic fabrics and other materials are produced from plant matter and other sources. Such materials may allow clothing manufacturers to reduce use of synthetic fabric such as polyester, made using fossil fuels. Algae and industrial waste products are two sources of biomatter being studied for further development of biosynthetic manufacturing.
Careers and Course Work
A bachelor of science degree is adequate training for an entry-level position in the biosynthesis field, but a master's of science or a doctorate is required to have the opportunity to lead research project teams in research and development, whether in academia, industry, or government. Because the field of biosynthetics involves several disciplines, college courses in chemistry, biology, genetics, microbiology, biochemistry, biomedical engineering, molecular biology, or biochemical engineering are the most helpful. Degrees in any of these disciplines would be appropriate preparation for entry into the biosynthetic field
Many researchers with a doctorate in one of the appropriate fields work in academia and teach while pursuing research. Many more employment opportunities in the pharmaceutical industry require a bachelor's or master's of science. These positions are in research and development and various areas of manufacturing, including quality control, quality assurance, and process development. There are also opportunities for technicians without a bachelor's degree. Technicians primarily record and analyze data while monitoring experiments and are often responsible for laboratory equipment maintenance.
Social Context and Future Prospects
The Human Genome Project has facilitated the mapping of genes, which has been instrumental in developing vaccines to treat influenza, cervical cancer, and malaria and creating new diagnostic tools for analysis. As a result, the pharmaceutical industry in the United States has become a multibillion-dollar industry. The generation of biosynthetic products has enhanced the lives of thousands of people by developing treatments for many types of cancer, pneumonia, cardiovascular diseases, diabetes, tuberculosis, neurological disorders, strokes, blood disorders, and many other diseases.
Combinatorial chemistry has allowed for rapid screening of potentially successful medications that may enhance and extend many lives. Normally, only one out of every 5,000 to 10,000 compounds screened makes it through the multiyear process of clinical trials to become an FDA-approved drug. However, the desire to recoup the money spent during the years of research required to bring a drug to market has caused some pharmaceutical companies to launch a product as early as possible, resulting in serious litigation because some drugs proved to have harmful side effects. The application of biosynthetic growth hormones for nonmedical applications, such as bodybuilding, has also caused ethical and medical controversy. However, as Earth’s population continues growing and the percentage of older adults increases, the need for the products of biosynthetic research will continue to grow.
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