The molecular structure of Nisin

Nisin, a natural bioactive antimicrobial peptide composed of 34 amino acids, has a unique molecular structure closely associated with its antimicrobial function. The following is an analysis of its molecular structure and antimicrobial mechanisms:

Amino Acid Composition and Special Structures

Nisin’s molecular structure contains 5 rare amino acids: lanthionine (ABA), dehydroalanine (DHA), dehydrobutyrine (DHB), alanine-thio-alanine (ALA-S-ALA), and alanine-thio-lanthionine (ALA-S-ABA). These rare amino acids form five internal cyclic structures via thioether bonds. This special cyclic structure endows Nisin with high stability and unique biological activity.

Molecular Domains

Nisin has two characteristic domains: the C-terminus and the N-terminus. The C-terminus consists of two thioether rings (D and E), while the N-terminus contains three thioether rings (A, B, and C). The two domains are linked by a flexible hinge region. This structure gives Nisin a high isoelectric point (pH 9), meaning it carries a positive charge across a wide pH range. However, solubility and antimicrobial activity decrease as pH increases.

Isomer Differences

Nisin exists in multiple isomeric forms, with 6 identified types (A, B, C, D, E, Z) to date. Among them, Nisin A and Nisin Z have been most actively studied. Their only difference lies in the 27th amino acid: Nisin A contains histidine (His), while Nisin Z contains asparagine (Asn). Generally, Nisin Z exhibits higher solubility and stronger antimicrobial activity than Nisin A.

Antimicrobial Mechanism

Nisin exerts its antimicrobial effect through the following steps:

As a cationic peptide, Nisin first binds to anionic components on bacterial cell walls (such as teichoic acid, lipoteichoic acid, acidic polysaccharides, or phospholipids) via hydrophobic or electrostatic interactions.

Its N-terminal region then selectively targets lipid II, a key precursor of bacterial cell wall synthesis. Nisin binds to lipid II, assembling into a "pore-forming complex" consisting of 4 Nisin molecules and 8 lipid II molecules. This complex forms stable pores in the bacterial cell membrane.

These pores cause rapid leakage of intracellular ions and cytoplasmic fluids, disrupting energy production and leading to bacterial death. Additionally, Nisin may directly induce cell wall lysis, further contributing to bacterial elimination.

Thanks to its unique molecular structure, Nisin effectively inhibits Gram-positive bacteria, including Lactobacillus, Clostridium botulinum, Staphylococcus, and Listeria—particularly spore-forming bacteria. As a natural antimicrobial substance with high safety, it is widely used in food preservation and other fields.