You probably know about the distinction between proteins and peptides: peptides being sequences typically made up of no more than 40 amino acids; proteins typically being no fewer than 150 amino acids. However, the sequences with between 40 and 150 amino acids have their own unique properties and are difficult to produce using conventional methods. Numaferm, a company focusing on developing the whole spectrum of amino acid based biologics, calls these in-between molecules ‘pepteins’.
Christian Schwarz is a cofounder of Numaferm, whose production platform Numatech is designed to produce peptides, proteins, and pepteins with high purity regardless of sequence length or functionality. Numatech comprises two core technologies: Numasec and Numaswitch.
Numasec, developed over a decade ago, was initially used to secrete proteins from E. coli. Target proteins are genetically fused to a ‘Sectag’ protein while co-expressing a transport complex, these proteins can then be secreted from Gram-negative bacteria like E. coli. This worked well but was eventually phased out due to the inefficiencies of recombinant processes compared to chemical synthesis.
However, the discovery that Sectag proteins become highly soluble upon binding with calcium ions led to the development of a new biochemical production platform, Numaswitch, which leverages this property. This technology allows for the efficient production of peptides, proteins, and pepteins by preventing intermolecular interactions during the refolding process, ensuring high purity and functionality.
However, Numaferm still needed to deal with the fact that these proteins would still be connected to the Switchtag. So, they developed the Numacut TEV protease to efficiently cleave Switchtag proteins from targets without leaving residues, enabling the production of pure functional proteins.
Schwarz then outlined how Numaswitch technology has been successfully applied to produce various functional proteins, including antimicrobial peptides, growth factors, and complex proteins with multiple disulfide bonds. Numaferm offers fast production timelines, handling short peptides to proteins up to 600 amino acids, with capabilities for milligram to kilogram batches and scalable approaches.