Rational design of hyperstable antibacterial peptides for food preservation

Website Link (Journal by Vishweshwaraiah et. al.)


We describe the design of peptides with properties like thermostability, pH stability, and antibacterial activity against a few bacterial food pathogens. Insights obtained from classical structure-function analysis of natural peptides and their mutants through antimicrobial and enzymatic assays are used to rationally develop a set of peptides. pH and thermostability assays were performed to demonstrate robust antimicrobial activity post-treatment with high temperatures and at wide pH ranges.

We have also investigated the mode of action of these hyperstable peptides using membrane permeability assays, electron microscopy, and molecular dynamics simulations.

Notably, through mutational studies, we show that these peptides elicit their antibacterial action via both membrane destabilization and inhibition of intracellular trypsin—the two functions attributable to separate peptide segments.

Finally, toxicity studies and food preservation assays demonstrate the safety and efficacy of the designed peptides for food preservation.

Overall, the study provides a general ‘blueprint’ for the development of stable antimicrobial peptides (AMPs). Insights obtained from this work may also be combined with combinatorial methods in high-throughput studies for future development of antimicrobials for various applications.


In this study, we attempt to design possible alternatives to antimicrobial peptides like Nisin. We ‘rationally’ develop new peptides that simultaneously possess multiple properties like stability at a broad range of pH, thermostability, and anti-trypsin activity. Bowman–Birk inhibitors (BBIs) are a class of serine protease inhibitors that are highly stable28.

These contain a conserved nine-residue loop responsible for protease inhibitory activity. Various BBIs are already being used to contain insect growth29 and for therapeutic applications28,30,31,32,33,34,35.

Based on our analysis of the structure and activity of this peptide class, our design strategy involves recognizing and incorporating multiple ‘desirable properties’ to obtain robust antibacterial agents with high stability. Preliminary studies suggest that these peptides are safe and could in principle be employed to increase the shelf life of food products. We also attempt to decipher their mode of action.

Molecular dynamics (MD) simulation studies on the peptide-membrane complex shed light on the underlying peptide-membrane interactions that result in the antimicrobial action.

Overall, this study provides insights into the mechanism of action of such class of peptides and demonstrates how multiple properties can be rationally incorporated to develop superior antibacterial peptides. Most importantly, some of these insights are broadly applicable to the design of antimicrobials for clinical and biomedical applications, in addition to food preservation.

Published by RenSun Lee

Kia ora! Sustainability is at the core of my soul ever since I was a kid. I always strive to finish the food on my plate and live as a minimalist. I love to cut down on waste in order to live sustainably and harmoniously with our planet. This brings me to my passion as a Food Scientist to integrate new technologies into innovative and creative solutions to meet customer demands and market trends and to optimize products and processes for quality, savings and sustainability. To these goals, I have published a Journal on my work on sustainable packaging and patented a new Antimicrobial wash. Nothing is more satisfying than working hard and smart at the workplace and playing hard outside of working hours. I enjoy rejuvenating myself through spending quality time with my two adorable kids and my awesome soul mate and getting close to nature when possible, be it gardening, tramping or going to the beach. I also love to learn about our magnificent universe and how sustainability is working in the grand scheme of things. I strongly believe that Work, Life & Balance is the key to a healthy state of mind, both physically and mentally. I look forward to making a positive difference wherever and whenever I can. Through this Blog, I hope to catalog recent Food Trends and Food Technologies that I come across so that anyone who is interested can have access to it (articles and resources). Please use these resources at your discretion. On top of that, I would also like to share related news and technologies of the future that would help mankind advance towards a Type 1 Civilization. Please feel free to contact me if you would like to share and contribute to the “Resources“. I would like to thank you in advance for dropping by. I sincerely hope that you can benefit from the recent Food Trends and Food Technologies I catalogued. Kind regards | Ngā mihi RenSun Lee

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