Peptide synthesis: chemical or enzymatic

Fanny Guzmán
Instituto de Biología
Pontificia Universidad Católica de Valparaíso
Avenida Brasil 2950
Valparaíso, Chile
Fax: 56 32 212746
E-mail: fanny.guzman@ucv.cl

Sonia Barberis
Facultad de Química, Bioquímica y Farmacia
Universidad Nacional de San Luis
Ejército de los Andes 950 (5700)
San Luis, Argentina
E-mail: sbarberi@unsl.edu.ar

Andrés Illanes*
Escuela de Ingeniería Bioquímica
Pontificia Universidad Católica de Valparaíso
Avenida Brasil 2147
Fax: 56 32 2273803
E-mail: aillanes@ucv.cl

*Corresponding author

Financial support: This work was done within the framework of Project CYTED IV.22 Industrial Application of Proteolytic Enzymes from Higher Plants.

Keywords: enzymatic synthesis, peptides, proteases, solid-phase synthesis.

Peptides are molecules of paramount importance in the fields of health care and nutrition. Several technologies for their production are now available, among which chemical and enzymatic synthesis are especially relevant. The present review pretends to establish a non-biased appreciation of the advantages, potentials, drawbacks and limitations of both technologies. Chemical synthesis is thoroughly reviewed and their potentials and limitations assessed, focusing on the different strategies and challenges for large-scale synthesis. Then, the enzymatic synthesis of peptides with proteolytic enzymes is reviewed considering medium, biocatalyst and substrate engineering, and recent advances and challenges in the field are analyzed. Even though chemical synthesis is the most mature technology for peptide synthesis, lack of specificity and environmental burden are severe drawbacks that can in principle be successfully overcame by enzyme biocatalysis. However, productivity of enzymatic synthesis is lower, costs of biocatalysts are usually high and no protocols exist for its validation and scale-up, representing challenges that are being actively confronted by intense research and development in this area. The combination of chemical and enzymatic synthesis is probably the way to go, since the good properties of each technology can be synergistically used in the context of one process objective.