Part:BBa_K5057005
CONGA Q7 antimicrobial peptide
Based on the research article by Ghimire et al. (2023) and a presentation by Prof. Dr. William Wimbley, iGEM Freiburg 2024 translated the peptide sequence of a synthethically produced antimicrobial peptide called d-CONGA-Q7 into a DNA sequence and optimized it for expression in E. coli. Since in the original source, the synthetic peptide was created with D-aminoacids, the name comes with a prefix "D-" referring to the molecular configuration of the aminoacids. In the experiments of team Freiburg 2024, the peptide was synthesized in E. coli using the usual L-amino acids.
Usage and Biology
D-CONGA-Q7 was created in a process of continued molecular evolution exhibiting a potent antimicrobial activity against planktonic or biofilm-forming Gram-negative bacteria such as P. aeruginosa and E. coli [1]. it is a short peptide with an overall cationic charge and as such can be classified as antimicrobial peptide (AMP).
Antimicrobial peptides (AMPs) are a diverse class of small, naturally occurring peptides playing a crucial role in the innate immune response of various organisms. These peptides consist of 10 to 60 amino acids and are generally characterized by their net positive charge and the ability to disrupt microbial membranes, thereby exhibiting potent activity against a wide range of pathogens, including bacteria, fungi, viruses and parasites. Most AMPs target bacterial membranes by creating pores or disrupting the whole membranes in the detergent-like manner [2]. These modes of action rely on both the cationic properties of the AMP itself, and negatively charged bacterial membranes. The differences in lipid composition between the host and pathogen membranes enable the AMPs to achieve high specificity [3].
Ongoing research has led to the discovery of further categories of AMPs exhibiting inhibitory or disruptive effects on protein and DNA synthesis, cell division and biofilm formation. These peptides rely on various mechanisms involving enzyme inactivation, signaling disruption or induction of degradation processes [4, 5, 6, 7].
Due to their extraordinary characteristics, AMPs constitute a promising research field for the development of new therapeutics to combat antibiotic resistance. Many attempts have been made to create synthetic AMPs de novo, mimicking the design of already existing peptides [8, 9, 10]. However, designing AMPs comes with several obstacles effectively preventing a wider use of AMPs in the medicine. As stated by Li et al.[2] AMPs often have a hemolytic effect on eukaryotic cells, they lack stability due to limited pH tolerance and proteolyse susceptibility and experience reduced activity in the presence of iron and different serums. A further limitation is also high costs of AMP production typically by chemical synthesis [11, 3].
Sequence and Features
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000COMPATIBLE WITH RFC[1000]
References
[1] Ghimire J, Hart RJ, Soldano A, Chen CH, Guha S, Hoffmann JP, et al. Optimization of Host Cell-Compatible, Antimicrobial Peptides Effective against Biofilms and Clinical Isolates of Drug-Resistant Bacteria. ACS Infectious Diseases [Internet]. 2023 Mar 24 [cited 2024 Sep 23];9(4):952–65.
[2] Huan Y, Kong Q, Mou H, Yi H. Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields. Frontiers in Microbiology [Internet]. 2020 Oct 16;11.
[3] Li J, Koh JJ, Liu S, Lakshminarayanan R, Verma CS, Beuerman RW. Membrane Active Antimicrobial Peptides: Translating Mechanistic Insights to Design. Frontiers in Neuroscience. 2017 Feb 14;11.
[4] Mardirossian M, Pérébaskine N, Benincasa M, Stefano Gambato, Hofmann S, Huter P, et al. The Dolphin Proline-Rich Antimicrobial Peptide Tur1A Inhibits Protein Synthesis by Targeting the Bacterial Ribosome. 2018 May 17;25(5):530-539.e7.
[5] He SW, Zhang J, Li NQ, Zhou S, Yue B, Zhang M. A TFPI-1 peptide that induces degradation of bacterial nucleic acids, and inhibits bacterial and viral infection in half-smooth tongue sole, Cynoglossus semilaevis. Fish & Shellfish Immunology [Internet]. 2017 Jan 1;60:466–73.
[6] Lutkenhaus J. Regulation of cell division in E. coli. Trends in Genetics. 1990;6:22–5.
[7] Li L, Sun J, Xia S, Tian X, Cheserek MJ, Le G. Mechanism of antifungal activity of antimicrobial peptide APP, a cell-penetrating peptide derivative, against Candida albicans: intracellular DNA binding and cell cycle arrest. Applied Microbiology and Biotechnology. 2016 Jan 8;100(7):3245–53.
[8] Goormaghtigh E, Meutter J, Szoka F, Cabiaux V, Parente RA, Ruysschaert JM. Secondary structure and orientation of the amphipathic peptide GALA in lipid structures. An infrared-spectroscopic approach. European Journal of Biochemistry. 1991 Jan;195(2):421–9.
[9] Fjell CD, Hiss JA, Hancock REW, Schneider G. Designing antimicrobial peptides: form follows function. Nature Reviews Drug Discovery. 2011 Dec 16;11(1):37–51.
[10] Jenisha G, Hart RJ, Soldano A, Chen CH, Guha S, Hoffmann JP, et al. Optimization of Host Cell-Compatible, Antimicrobial Peptides Effective against Biofilms and Clinical Isolates of Drug-Resistant Bacteria. ACS Infectious Diseases [Internet]. 2023 Mar 24;(4):952–65.
[11] Jaradat DMM. Thirteen decades of peptide synthesis: key developments in solid phase peptide synthesis and amide bond formation utilized in peptide ligation. Amino Acids. 2017 Nov 28;50(1):39–68.
| None |