Activity and Export of Engineered Nisin-(1-22) Analogs

Abstract

Abstract:The pentacyclic peptide antibiotic nisin, produced by Lactococcus lactis is ubiquitously applied as a food preservative. We previously demonstrated that the truncated nisin-(1-22) has only 10-fold lower activity than nisin. Here we aimed at further developing this tricyclic nisin analog to reach activity comparable to that of nisin. Our data demonstrate that: (1) ring A has a large mutational freedom; (2) the composition of residues 20-22 strongly affects production levels of nisin-(1-22); (3) a positively charged C-terminus of nisin-(1-22) significantly enhances its antimicrobial activity; (4) nisin-(1-22) inhibits in vitro growth of a target strain using different dynamics than nisin.

WITHDRAWN: Chemical Modification of Nisin With Homocysteine Thiolactone And Its Antibacterial Activity

“…Hence, it was hypothesized that the reduction of positive charges after homocysteinylation reduced the antibacterial activity of nisin. Additionally, newly introduced free -SH groups might react with dehydrobutyrine or dehydroalanine forming an intermolecular lanthionine bonds [31], causing a signi cant loss of antibacterial activity. The observed lower antibacterial activity after modi cation of nisin might also be due to the fact that the modi cation caused a signi cant structural change in nisin by adding free -SH groups.…”

Intensive Mutagenesis of the Nisin Hinge Leads to the Rational Design of Enhanced Derivatives

“…Although this is not the first study which has fully randomised the nisin ‘hinge’ region, it is the first to do so in the context of the full length nisin peptide. Previously, Plat and co-workers [28] randomised all three positions in a truncated form of nisin, i.e. nisin-(1–22), and found when they analysed 16 of the active derivatives that the size of the zone was directly, for the most part, proportional to the amount of the prepeptide produced.…”

Mimicry of a Non-ribosomally Produced Antimicrobial, Brevicidine, by Ribosomal Synthesis and Post-translational Modification

“…The dehydratase NisB, the cyclase NisC, and the transporter NisT constitute one of the best-studied lanthipeptide modification and secretion machineries, the nisin biosynthetic machinery (Figure S1) (Kuipers et al, 1995(Kuipers et al, , 1998De Ruyter et al, 1996;Zhao et al, 2020a). This biosynthetic machinery has been widely and successfully used in producing designed lanthipeptides and for screening potent genetically encoded libraries of lanthipeptides (Bosma et al, 2011;van Heel et al, 2013van Heel et al, , 2016Li et al, 2018a;Majchrzykiewicz et al, 2010;Moll et al, 2010;Plat et al, 2011;Rink et al, 2007;Schmitt et al, 2019;Urban et al, 2017).…”