About This Project

Inspired by traditional medicine and the engineering paradigm, and armed by modern synthetic biology tools and methods, we aim to create a tool for the production of synthetic cyclic peptides and screen their antimicrobial properties to pave the way for further development of new medicinals.

An iGEM project from Latvia, Riga focusing on BURP domain protein expression in E. coli to produce cyclic peptides as antimicrobials.

Ask the Scientists

What is the context of this research?

Plant cyclic peptides are circularised short amino acid peptides that form a wide variety of natural compounds. They exhibit exceptional stability, cell membrane penetration, and diversifiability, showing great potential as alternatives to existing broad-spectrum and non-specific antibiotics.

In recent years, efforts have been made to characterise the mechanisms of synthesis of cyclic peptides. Notably, various plants have been shown to have BURP domain-containing proteins that can cleave the tail of the corresponding peptide and cyclize it, creating a biologically active cyclic peptide. This opens up new opportunities in research, because BURP domain proteins could be conjugated with various synthetic peptides to form novel medicinal substances with unique properties.

What is the significance of this project?

Antimicrobial resistance is a growing concern worldwide, leading to the emergence of incurable diseases. Right now it's 700,000 deaths per year, but a 2050 estimate stands at 10 million. New antibiotics take decades to create - while bacteria can develop resistance in 2-3 years. Therefore it is necessary to explore and develop alternatives to classical antibiotics, whose extensive use has contributed to this problem.

Cyclic peptides are known for their antimicrobial properties and can help combat the global surge of antimicrobial resistance. Furthermore, they can be a strong basis for developing novel antiviral and anti-cancer drugs. Their efficacy against plant pathogens proves them to be potent pesticides with applications in agriculture.

What are the goals of the project?

The main objective of our iGEM project is to demonstrate the utility of the BURP domain protein as a synthetic biology tool for generating therapeutic cyclic peptides.

Starting with recombinant protein expression in E. coli, we have moved on to protein purification using different fusion tags. We plan on performing cyclisation experiments on the purified BURP proteins both by changing the core peptide sequences already connected to the BURP domain and adding separate linear peptides as a cyclisation substrate. The peptides produced during our project will be tested in mass spectrometry and on various plant and human pathogenic fungi and bacteria.

We hope that our project can serve as a foundational advance for the development of cyclic peptides tailored for different purposes.