Cangene Corporation

Eva Walcyzk

Lawrence T Malek

Daniel Bartfeld

Dany Hadary

Gisela Soostmeyer

David L Jenish

Timothy J Krieger

Michael J Butler

A family of proteases endogenous to Streptomyces cells degrade heterologous proteins secreted from Streptomyces host cells. The previously unidentified proteases include (1) tripeptidyl aminopeptidase--Streptomyces ('Tap'), (2) a Streptomyces protease ('Ssp') which displayed significant amino acid sequence homology to Subtilisin BPN' and showed an ability to remove tripeprides from the amino termini of proteins and peptides, and (3) other proteases derived from Streptomyces which degraded certain substrates under certain conditions. Degradation was alleviated by selective inhibition of secreted proteases or by using hosts with impaired capabilities to produce proteases. An irreversible inhibitor was designed based upon the mechanism and substrate specificity of the target protease. Hosts secreting high amounts of proteases were selected. Impaired hosts were produced by deleting or altering the nucleotide sequence for the proteases.

Streptomyces proteases and improved streptomyces strains for expression

Growing community of inventors

Mississauga, Canada

Eva Walcyzk