Lanthipeptides: chemical synthesis versus in vivo biosynthesis as tools for pharmaceutical production.
Lanthipeptides (also called lantibiotics for those with antibacterial activities) are ribosomally synthesized post-translationally modified peptides having thioether cross-linked amino acids, lanthionines, as a structural element. Lanthipeptides have conceivable potentials to be used as therapeutics, however, the lack of stable, high-yield, well-characterized processes for their sustainable production limit their availability for clinical studies and further pharmaceutical commercialization. Though many reviews have discussed the various techniques that are currently employed to produce lanthipeptides, a direct comparison between these methods to assess industrial applicability has not yet been described. In this review we provide a synoptic comparison of research efforts on total synthesis and in vivo biosynthesis aimed at fostering lanthipeptides production. We further examine current applications and propose measures to enhance product yields. Owing to their elaborate chemical structures, chemical synthesis of these biomolecules is economically less feasible for large-scale applications, and hence biological production seems to be the only realistic alternative.
Chair of Bioprocess Engineering, Department of Biotechnology, Technische Universität Berlin, Ackerstraße 76, ACK24, 13355, Berlin, Germany. elvis.ongey2@gmail.com.
Elvis Legala
http://orcid.org/0000-0002-4554-1359
EL
Ongey
Chair of Bioprocess Engineering, Department of Biotechnology, Technische Universität Berlin, Ackerstraße 76, ACK24, 13355, Berlin, Germany.
Peter
P
Neubauer
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000138:chemical synthesis* / Q000494:pharmacology; D001430:Bacteriocins / Q000096:biosynthesis* / Q000138:chemical synthesis* / Q000494:pharmacology; D057005:Bioengineering / Q000191:economics; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D005810:Multigene Family; D010455:Peptides / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D060327:Solid-Phase Synthesis Techniques / Q000191:economics
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D010455:Peptides
Bioengineering; Bioprocess; Economic; Enfuvirtide; Industrial; Lanthipeptide; Large-scale; Ruminococcin