Phage Lysin Bioengineering

Lysins are a class of phage-derived peptidoglycan hydrolases proven to kill bacteria rapidly. In this era of the increasing prevalence of drug-resistant pathogens, phage lysin bioengineering is emerging as a research focus. As a leader in the field of lysins research, Creative Biolabs specializes in providing one-stop services for the development of engineered lysins, escorting your engineered lysins projects.

Overview of Phage Lysin Bioengineering

Compared with antibiotics, phage lysins possess some desirable properties, including high specificity and activity against multidrug-resistant pathogens, novel antibacterial mechanisms, and a low likelihood of drug resistance. At the same time, the modular structure of lysins facilitates the design of lysins with specific characteristics, including a broader killing spectrum, higher activity, and improved solubility. In conclusion, engineered lysins represent a crucial strategy to combat antimicrobial resistance in the context of growing drug resistance. Therefore, the development of engineered lysins contributes to the creation of novel enzymatic organisms with improved lytic activity and profiles against various bacterial pathogens and provides new directions for exploring the modular evolution of lysins.

Fig.1 Lysin-based murein hydrolases.^1,3

Engineered Lysins

• Chimeolysin

Lysins typically contain two domains: a catalytic domain (CD) and a cell wall-binding domain (CBD). Traditionally, the CD was thought to be involved only in peptidoglycan hydrolysis, whereas CBD determined the cleavage profile of lysins. Both domains can be shuffled from various native lysins to construct chimeric lysins due to the modular structure of lysins. Chimeric lysins are characterized by improved cleavage activity, enhanced solubility, or expanded cleavage profiles. Therefore, engineered chimeolysins offer a promising prospect for finding lysins with improved properties.

Fig.2 Screening of bactericidal chimeolysins.^2,3

• Artificial Lysin

Artificial lysins, are produced by fusing natural lysin fragments with peptides or proteins. A typical example is to design artificial lysins against Gram-negative bacteria. As is known, natural lysins only lyse Gram-positive bacteria exogenously, but some lysins after artificial modification can kill Gram-negative bacteria directly. Therefore, the development of engineered lysins may contribute to the production of lysins that target different bacterial pathogens. The phage lysins could also be modified to change the plasma half-life. In general, the half-life of lysins is relatively short. Prolonging the residence time of lysin in vivo requires modification of the Fc region of polyethylene glycol or immunoglobulin G (IgG). At present, modified long-acting lysins have achieved success. For example, studies have shown that modified lysins can be added directly into the intrathecal brain to treat meningitis.

Services at Creative Biolabs

Creative Biolabs has a professional phage lysin bioengineering research team, keeping up with the latest advances in lysin research. We have developed an advanced lysin engineering platform to efficiently design better lysins, such as artificial lysins, chimeolysins, and modified long-acting lysins by utilizing the modular structural features of lysins to help global customers conduct cutting-edge lysin research. Creative Biolabs provides the most comprehensive and professional lysin bioengineering services to customers around the world. We also offer custom services to meet all your research and development needs. For more information, please feel free to contact us.

References:

1. Yang, H.; et al. Engineered bacteriophage lysins as novel anti-infectives. Frontiers in microbiology. 2014, 5: 524.
2. Yang, H.; et al. A chimeolysin with extended-spectrum streptococcal host range found by an induced lysis-based rapid screening method. Scientific reports. 2015, 5(1): 1-12.
3. under Open Access license CC BY 4.0, without modification.