What are Amino Acids Made of?

Organic substances known as amino acids serve as the building blocks of proteins and are essential to many biological processes in living things. Amino acids are utilized in the pharmaceutical, food additive, animal feed, and cosmetics industries. There are multiple processes involved in the industrial preparation of amino acids. Amino acids can first be made through fermentation or chemical synthesis. While fermentation uses microorganisms like bacteria or fungi to digest sugars or other organic substrates into amino acids, chemical synthesis uses sophisticated chemical reactions to create amino acids from basic organic components.

Amino Acid Backbone

Amino acids are organic compounds composed of carbon, hydrogen, oxygen, and nitrogen atoms, and some amino acids also contain sulfur atoms. The central carbon atom in an amino acid is bonded to hydrogen atoms, amino groups (NH2), carboxyl groups (COOH), and side chains (R groups) that distinguish one amino acid from another. It is this unique side chain that gives each amino acid its unique properties and allows the diversity of proteins in nature to exist.

Properties of Amino Acids

There are 20 standard amino acids commonly found in proteins, each with its own specific side chain that determines its chemical properties and functions. These amino acids can be divided into different categories based on the characteristics of their side chains. There are two main categories: nonpolar amino acids, whose hydrophobic side chains do not interact easily with water, and polar amino acids, whose hydrophilic side chains interact well with water. In addition, amino acids can be further classified as acidic, basic, or neutral, based on the charge of the side chain.

• Nonpolar amino acids are important for forming the core of globular proteins and stabilizing protein structure through hydrophobic interactions. Examples of nonpolar amino acids include glycine, alanine, valine, leucine, isoleucine, proline, methionine, and phenylalanine.
• Polar amino acids are essential for maintaining protein solubility in water and promoting interactions with other molecules. These amino acids often participate in hydrogen bonds and play a key role in protein folding and stability. Examples of polar amino acids include serine, threonine, cysteine, tyrosine, asparagine, glutamine, and histidine.
• Acidic amino acids, such as aspartic acid and glutamic acid, have side chains that can release hydrogen ions (protons) in solution, making them negatively charged at physiological pH. Basic amino acids, such as lysine, arginine, and histidine, have side chains that can accept hydrogen ions, resulting in a positive charge at physiological pH. These charged amino acids play important roles in enzymatic reactions, protein-protein interactions, and maintaining the overall charge balance within the protein structure.
• There are more amino acids than the twenty common amino acids found in proteins. Other amino acids provide crucial biological roles even if they are not included in proteins. For instance, the urea cycle, which eliminates ammonia from the body, has intermediates in ornithine and citrulline. Furthermore, certain amino acids, including taurine and gamma-aminobutyric acid (GABA), can function as neurotransmitters and are crucial for brain transmission.

Amino Acid Synthesis

• Strecker Synthesis

In 1850, Strecker first used acetaldehyde, ammonia and HCN to react to obtain α-cyanamide, and then hydrolyzed it to obtain α-amino acids.

After Zelinsk's improvement, ammonium chloride and potassium cyanide were used instead of hydrocyanic acid and ammonia, thus avoiding the direct use of hydrogen cyanide or ammonium cyanide, and the same product was obtained after the reaction. When reacting with ammonium chloride, primary amines are generated; or when reacting with primary or secondary amines, substituted amino acids are generated. When reacting with ketones, α,α-disubstituted amino acids are obtained.

• Erlenmeyer Synthesis

Erlenmeyer synthesis is also called Erlenmeyer-Plöchl synthesis. It refers to the generation of dihydrooxazolone (azlactone) intermediates by α-amidoacetic acid in the presence of acetic acid or acetic anhydride, sodium acetate (or potassium carbonate). Since the methylene group on the intermediate oxazolone ring is affected by the adjacent carbonyl group, H has a certain acidity, and condenses with aldehyde under the action of alkali, and then reduces and hydrolyzes to obtain α-amino acids. The general reaction formula is as follows:

For example, the synthesis of α-phenylalanine:

First, glycine reacts with benzoyl chloride to generate benzoylglycine (commonly known as hippuric acid), and then benzoylglycine is cyclized under the action of acetic anhydride, and a water molecule is removed to generate oxazolone (or dihydrooxazolone). The methylene H on the heterocyclic ring has a certain acidity, and condenses with benzaldehyde under alkaline conditions, and then catalytic hydrogenation is carried out, and finally hydrolysis is carried out to obtain the target product α-phenylalanine.

• Malonate Synthesis

The activity of the methylene group in the malonate molecule makes it widely used, and it can be used to synthesize α-amino acids.

• Halomalonate synthesis: Using halogenated (chloro or bromo) malonate and phthalimide, various α-amino acids can be synthesized. The general reaction formula is as follows:

• Acetylaminomalonate synthesis: The malonate is first nitrosated to generate oxime malonate, then reduced to generate acetylaminomalonate, and then reacted with alkyl halide under the action of sodium alcohol to generate α-substituted acetylaminomalonate, and finally alkaline hydrolyzed and acidified to obtain α-amino acids.

• Phase Transfer Catalytic Synthesis

In the presence of alkaline, phase transfer catalysts [such as triethylbenzylammonium chloride (TEBA)], Schiff bases generated by aldehydes and amines can undergo alkylation reactions with alkyl halides (such as RCl, RBr, etc.) to produce amino acids. This method can be used to synthesize alanine, phenylalanine, methionine, tryptophan, aspartic acid, leucine, orthovaline, valine, norleucine, etc. For example: R=H, R′=Bn, phenylalanine can be synthesized; R′=CH3, glycine can be synthesized.

Amino Acid Fermentation

With the application of gene editing technology and comprehensive synthetic biology, the production of amino acids by fermentation is becoming increasingly advantageous. Compared with chemical synthesis, fermentation has many advantages, including higher efficiency, lower production costs and environmental sustainability. At present, the main strains used for amino acid fermentation are Corynebacterium glutamicum, Brevibacterium flavum, Brevibacterium lactofermentum, Bacillus brevis, and Sesinobacterium marcescens. The key steps of amino acid fermentation include:

1. Selection of microorganisms: The first step in the fermentation process is to select suitable microorganisms that can produce the required amino acids. Different microorganisms have specific metabolic pathways for amino acid synthesis, and the selection of strains depends on factors such as productivity, substrate utilization, and environmental conditions.

2. Fermentation medium preparation: Once the microorganism is selected, a fermentation medium containing nutrients such as carbon source, nitrogen source, minerals and vitamins is prepared. These nutrients provide basic building blocks for amino acid synthesis and support the growth and metabolism of microorganisms.

3. Inoculation: The selected microorganism is then inoculated into the fermentation medium under controlled conditions. The inoculum size, temperature, pH and oxygen level are carefully optimized to promote the growth and metabolic activity of the microorganism.

4. Fermentation process: The fermentation process is divided into several phases, including the lag phase, exponential growth phase, stationary phase, and decay phase. During the exponential growth phase, the microorganisms synthesize amino acids through specific metabolic pathways, utilizing nutrients present in the fermentation medium.

5. Harvesting: After the fermentation process is complete and the desired amino acids are synthesized, the culture broth is harvested. The harvested culture broth is then processed to separate and purify the amino acids from the fermentation medium using techniques such as filtration, precipitation, and chromatography.

6. Downstream processing: The final step in the fermentation process is downstream processing, which involves further purification and concentration of the amino acids to meet quality standards. This may include additional filtration, ion exchange chromatography, and crystallization to obtain the amino acids in pure form.

Amino Acids from BOC Sciences

Based on this, BOC Sciences offers a wide range of amino acids, including natural, standardized, modified and rare amino acids, in both small and large quantities. This supply flexibility enables BOC Sciences to meet orders of all sizes, from research laboratories requiring small quantities for experiments to large production facilities requiring large quantities for manufacturing processes.

What Does Amino Acids Do?

Because of their special qualities and purposes, amino acids are not only the building blocks of proteins in living things but also essential components of many industrial uses. Aside from their biological roles, amino acids are utilized in biotechnology, medicines, cosmetics, food and beverage production, and agriculture. The fact that amino acids can be used as raw materials for chemical synthesis and bioprocessing further demonstrates their adaptability in industrial applications. Amino acids are building blocks of many other compounds, such as peptides, derivatives of amino acids, and amino alcohols. Amino acids can be fermented to produce high-value molecules including bioactive peptides, sweeteners, and taste compounds utilizing microorganisms or enzyme biocatalysts. These bio-based chemicals offer environmentally friendly alternatives to traditional petrochemical-derived products, contributing to sustainable industrial practices.

• Amino Acids for Food Industry

The food and beverage business is one area where amino acids are widely used in industry. A wide range of food products use amino acids as nutritional supplements, flavor enhancers, and preservatives. For instance, the sodium salt of glutamic acid known as monosodium glutamate (MSG) is frequently employed as a flavor enhancer to improve the flavor of a variety of processed foods. In order to enhance the nutritional condition of cattle overall and encourage growth, amino acids like methionine and lysine are also given to animal feed. Moreover, sports nutrition supplements include amino acids like citrulline and arginine to improve muscle repair and athletic performance.

• Amino Acids for Drug Discovery

Amino acids are crucial building elements for a variety of medications and treatments in the pharmaceutical industry. Peptide medications, which are used to treat a wide range of illnesses and ailments, are made up of chains of amino acids. For instance, the peptide hormone insulin, which is made up of amino acids, is crucial for the control of diabetes. Moreover, amino acids are needed in the manufacture of medications used in chemotherapy, antivirals, and antibiotics. Amino acids are also added to medicinal formulations to increase stability, solubility, and bioavailability.

• Amino Acids for Cosmetics

Because amino acids have skin-repairing, anti-aging, and moisturizing qualities, they are frequently found in cosmetics and personal hygiene products. Amino acids that support skin hydration and suppleness, like arginine, proline, and serine, are frequently used in skin care products. The synthesis of collagen, which is necessary for the firmness and suppleness of skin, is also aided by these amino acids. Amino acids are also used to strengthen and repair damaged hair strands in hair care products. A vital component of hair care products that supports hair health and growth is keratin, a protein abundant in amino acids.

• Amino Acids for Agriculture

Amino acids are utilized in agriculture as plant growth regulators and fertilizers to raise crop yields and quality. Amino acid fertilizers improve nutrient uptake and utilization by giving plants the nutrients they need in an easily absorbed form. Additionally, they promote the growth of roots, flowers, and fruits in a variety of crops. As natural chelators, amino acids like glutamine and glycine aid in the more effective uptake of micronutrients by plants, including iron, zinc, and copper. Furthermore, amino acids are added to animal feed additives to enhance nutritional digestion and support healthy animal growth.

• Amino Acids for Biotechnology

Amino acids are used in a wide range of biotechnological activities, such as enzyme synthesis, protein engineering, and the creation of biofuels. The basic building blocks of genetic engineering methods, amino acids are utilized to alter and create recombinant proteins with particular characteristics and roles. Enzymes generated from amino acids are essential to several biocatalytic processes utilized in the bioremediation, medicine manufacturing, and biofuel generation industries. Bio-based polymers, biodegradable polymers, and other sustainable products are also made with amino acids.