# The Potential of Non-Ribosomal Peptide Engineering for Creating New Antimicrobial Complexes

**Authors:** Evgeniya V. Prazdnova, Maxim P. Kulikov, Ludmila E. Khmelevtsova

PMC · DOI: 10.3390/molecules31040683 · 2026-02-16

## TL;DR

This paper explores how non-ribosomal peptides can be engineered to create new antimicrobial complexes for fighting drug-resistant microbes.

## Contribution

The novelty lies in proposing non-ribosomal peptides as a promising alternative to ribosomal peptides for antimicrobial complex engineering.

## Key findings

- Non-ribosomal peptides have inherent properties suitable for antimicrobial applications.
- NRPs can be engineered to create advanced agents against antibiotic-resistant microorganisms.
- The review highlights structural and self-assembly features of NRPs relevant to antimicrobial activity.

## Abstract

Self-assembling antimicrobial complexes are a promising new technology for the development of antimicrobial, antifungal, and other bioactive agents with targeted delivery, adaptability, and the regulation of processes over time. Ribosomally synthesized antimicrobial peptides (AMPs) are most frequently considered as the basis for such complexes; however, we suggest that non-ribosomally synthesized peptides (NRPs) should be considered as molecules that also hold potential for engineering and already possess a set of qualities that AMPs are still to be engineered to have. This review examines the key features of NRP structure and self-assembly that determine their potential as antimicrobial agents, as well as NRP engineering methods through which new, more advanced agents for combating antibiotic-resistant microorganisms can be created.

## Full-text entities

- **Genes:** MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, PTPA (protein phosphatase 2 phosphatase activator) [NCBI Gene 5524] {aka PARK25, PP2A, PPP2R4, PR53}, SOAT1 (sterol O-acyltransferase 1) [NCBI Gene 6646] {aka ACACT, ACAT, ACAT-1, ACAT1, SOAT, STAT}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CAMP (cathelicidin antimicrobial peptide) [NCBI Gene 820] {aka CAP-18, CAP18, CRAMP, FALL-39, FALL39, HSD26}, HNP1 (Hypertensive nephropathy) [NCBI Gene 574045], CYP4F3 (cytochrome P450 family 4 subfamily F member 3) [NCBI Gene 4051] {aka CPF3, CYP4F, CYPIVF3, LTB4H}, PGPEP1 (pyroglutamyl-peptidase I) [NCBI Gene 54858] {aka PAP-I, PGI, PGP, PGP-I, PGPI, Pcp}, CS (citrate synthase) [NCBI Gene 1431]
- **Diseases:** death (MESH:D003643), carcinogenic (MESH:D011230), infected (MESH:D007239), postoperative complications (MESH:D011183), cytotoxicity (MESH:D064420), bacterial (MESH:D001424), Gram-negative infections (MESH:D016905), nephro-, neuro- or myotoxicity (MESH:D000081030), fungal (MESH:D009181), NRPs (MESH:C565529), MRSA (MESH:D013203), injury to (MESH:D014947), inflammation (MESH:D007249), mitochondrial dysfunction (MESH:D028361), T-cell toxicity (MESH:D016411), neurotoxic (MESH:D020258), cancer (MESH:D009369), testicular cancer (MESH:D013736), Hodgkin's disease (MESH:D006689), hemolysis (MESH:D006461)
- **Chemicals:** BocK (-), Orn (MESH:D009952), salmochelin (MESH:C000630262), K+ (MESH:D011188), actinomycin (MESH:D003609), Na+ (MESH:D012964), chaetomin (MESH:C001598), Cyclosporin A (MESH:D016572), bialaphos (MESH:C003122), cyclo(L-Phe-trans-4-OH-L-Pro (MESH:C466305), disulfide (MESH:D004220), aspartic acid (MESH:D001224), -amino acids (MESH:D000596), pyoverdine (MESH:C042453), alamethicin (MESH:D000408), macrolide (MESH:D018942), Ser (MESH:D012694), phenylalanine (MESH:D010649), jadomycin B (MESH:C081750), fatty acid (MESH:D005227), tedizolid (MESH:C546016), Mg-ATP (MESH:D000255), Daptomycin (MESH:D017576), polyene (MESH:D011090), Lipopeptides (MESH:D055666), sirodesmin (MESH:C014187), Glycopeptide (MESH:D006020), LPS (MESH:D008070), lactones (MESH:D007783), lipid (MESH:D008055), Cys (MESH:D003545), thaxtomin A (MESH:C406691), sevadicin (MESH:C000590643), acetate (MESH:D000085), potassium chloride (MESH:D011189), lysine (MESH:D008239), roquefortine (MESH:C012536), beta-lactam (MESH:D047090), guanosine (MESH:D006151), tryptophan (MESH:D014364), peptaibols (MESH:D054848), iturin A (MESH:C013579), Hydrogen (MESH:D006859), verruculogen (MESH:C009658), bacitracin (MESH:D001414), Thr (MESH:D013912), calcium (MESH:D002118), Metal (MESH:D008670), bacillomycin (MESH:C020977), teicoplanin (MESH:D017334), EPS (MESH:C100219), azithromycin (MESH:D017963), JBIR-06 (MESH:C530710), nitrate (MESH:D009566), acid (MESH:D000143), enterobactin (MESH:D004758), oxazolidinone (MESH:D023303), AMP (MESH:D000089882), zinc (MESH:D015032), yersiniabactin (MESH:C104398)
- **Species:** Xenorhabdus szentirmaii (species) [taxon 290112], Staphylococcus aureus (species) [taxon 1280], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Mycobacterium (genus) [taxon 1763], Trichoderma (genus) [taxon 5543], Homo sapiens (human, species) [taxon 9606], Acinetobacter baumannii (species) [taxon 470], Burkholderia thailandensis (species) [taxon 57975], Bacillus subtilis subsp. subtilis (subspecies) [taxon 135461], Bacillus (genus) [taxon 55087], Aspergillus (genus) [taxon 5052], Drosophila melanogaster (fruit fly, species) [taxon 7227], Escherichia coli (E. coli, species) [taxon 562], Salmonella (genus) [taxon 590], Bacillus subtilis (species) [taxon 1423], Paenibacillus polymyxa (species) [taxon 1406], Pseudomonas aeruginosa (species) [taxon 287], Caenorhabditis elegans (species) [taxon 6239], Bacillus amyloliquefaciens (species) [taxon 1390], Klebsiella pneumoniae (species) [taxon 573], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Streptomyces venezuelae (species) [taxon 54571]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12943608/full.md

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Source: https://tomesphere.com/paper/PMC12943608