Post-translational modification in the biosynthesis of Nisin

Nisin is an antimicrobial peptide produced by Streptococcus lactis, and the post-translational modification process in its biosynthesis is relatively complex yet critical. The specific process is as follows:

Dehydration Reaction

First, the precursor peptide of nisin (Prenisin) undergoes post-translational modification under the action of the dehydratase NisB. NisB can specifically recognize serine (Ser) and threonine (Thr) residues in the precursor peptide, dehydrate them, and convert them into dehydroalanine (DHA) and dehydrobutyrine (DHB), respectively. This process is a fundamental step for Nisin to form its unique structure and function, laying the groundwork for the subsequent cyclization reaction.

Cyclization Reaction

After the dehydration reaction, the cyclase NisC catalyzes a reaction between the dehydrated amino acid residues (DHA and DHB) and cysteine (Cys) residues to form thioether bonds, thereby generating lanthionine (Lan) and methyllanthionine (MeLan). These thioether ring structures are the characteristic structures of nisin, endowing it with unique stability and antibacterial activity. A nisin molecule typically contains five such thioether rings, designated as rings A, B, C, D, and E.

Transport and Cleavage

The precursor peptide modified by dehydration and cyclization is transported outside the cell under the action of the ABC transporter protein NisT. Subsequently, the extracellular protease NisP cleaves the leader peptide of the precursor peptide, releasing the active mature nisin molecule.

Synergistic Effect of the Modification System

Proteins such as NisB, NisC, and NisT may form a membrane-associated lantibiotic synthetase complex, which collectively participates in the post-translational modification process of nisin. Studies have found that NisB and NisT can be connected to each other through NisC to form a complex. The existence of this complex helps improve the efficiency and accuracy of the modification process.

Role of the Leader Peptide

The leader peptide plays an important role in the post-translational modification process of nisin. It is not only essential for the initial recognition and binding of the precursor peptide to modification enzymes (e.g., NisB) but may also be involved in regulating the progression of the modification process. For example, when specific sequences in the leader peptide undergo mutations, it may affect the binding of the precursor peptide to modification enzymes, thereby hindering the normal progression of the modification process.