Imported Nisin Raw Materials, functions and modification mechanisms of rare amino acids

Nisin is a polypeptide antibiotic produced by Streptococcus lactis. Its molecule contains two rare amino acids, lanthionine and β-methyl lanthionine. The following is an introduction to their functions and modification mechanisms:

I. Functions of Rare Amino Acids

1. Enhancement of Antibacterial Activity

Destruction of the Cell Membrane

The special cyclic structure formed by lanthionine and β-methyl lanthionine enables the Nisin molecule to embed into the phospholipid bilayer of the bacterial cell membrane. This embedding action forms pores in the cell membrane, destroying the integrity of the cell membrane and causing the leakage of intracellular substances, such as ions and small molecular compounds. Eventually, this leads to the death of bacteria.

Inhibition of Cell Wall Synthesis

Nisin can bind to key enzymes involved in the synthesis process of the bacterial cell wall, inhibiting the synthesis of peptidoglycan. As a result, it hinders the formation of the bacterial cell wall, preventing bacteria from maintaining their normal cell morphology and structure, and ultimately inhibiting bacterial growth.

2. Improvement of Stability

Resistance to Protease Degradation

The special chemical structures of lanthionine and β-methyl lanthionine endow Nisin with high stability. The presence of these rare amino acids enables Nisin to resist the degradation of various proteases, prolonging its half-life in the organism and ensuring its effectiveness in food preservation and anti-corrosion processes.

Tolerance to Harsh Environments

The rare amino acids in the Nisin molecule help enhance its tolerance to harsh environments such as high temperatures, acids, and alkalis. During food processing, under conditions such as high-temperature sterilization and acidic environments, Nisin can still maintain a certain level of activity and exert its antibacterial effect.

II. Modification Mechanisms of Rare Amino Acids

1. Synthesis of the Precursor Peptide

Gene Encoding and Transcription

The synthesis of Nisin is controlled by a series of genes encoded on the chromosome of Streptococcus lactis. First, the relevant genes synthesize the mRNA of the precursor peptide through the transcription process. Then, using the mRNA as a template, translation occurs on the ribosome to synthesize the precursor peptide of Nisin. The precursor peptide contains regions of the signal peptide, leader peptide, and mature peptide.

2. Dehydration Reaction

Action of Dehydratase

After the synthesis of the precursor peptide, specific dehydratases will carry out dehydration reactions on specific serine or threonine residues in the precursor peptide. These enzymes recognize specific sequences and structures in the precursor peptide and remove the hydroxyl groups of serine or threonine residues to form corresponding dehydrated amino acid intermediates. For example, serine forms dehydroalanine (Dha) after dehydration, and threonine forms dehydrobutyrine (Dhb) after dehydration.

3. Formation of Thioether Bonds

Catalysis by Cyclase

After the dehydration reaction is completed, the cyclase plays a role in catalyzing the reaction between the dehydrated amino acid intermediate and the adjacent cysteine residue to form a thioether bond. Specifically, the sulfhydryl group (-SH) of cysteine attacks the carbon-carbon double bond of the dehydrated amino acid intermediate, and a Michael addition reaction occurs, thus forming lanthionine or β-methyl lanthionine. If β-methyl lanthionine is formed, a specific methyltransferase is involved in the reaction process to transfer the methyl group to the corresponding amino acid residue.

4. Maturation and Secretion

Excision of the Leader Peptide

For the modified precursor peptide, its leader peptide will be excised by specific proteases, releasing the mature Nisin molecule. The mature Nisin is secreted outside the cell through the secretion system of bacteria to exert its antibacterial effect.