improved production of recombinant human activin a in escherichia coli

Activin a is a member of transforming growth factor β (tgf-β) superfamily. it plays numerous roles in the body such as cell growth regulation and differentiation, wound repairing and modulation of inflammatory responses. more importantly, it can be used as a therapeutic agent; so recombinant production of it, especially in the periplasm of e. coli as an economical bacterium is of great value. the aim of this study is large- scale production of activin a with a correct structure. for this purpose, three strategies were used. first, an efficient and appropriate signal peptide, modified iranian bacillus licheniformis α-amylase signal peptide, was selected to secrete activin a to the e. coli periplasm as a suitable environment for correct protein folding. second, cytoplasmic chaperones, dnak, dnaj, groel/ groes, tf (trigger factor) were expressed simultaneously with activin a. finally, the agitation rate was optimized to achieve the highest production of activin a at the bioreactor scale. our results indicated that by the co-expression of tf with activin a and using agitation rate of 1000 rpm maximum expression of activin a in e. coli was obtained. more importantly, based on the cd spectroscopy results and bioassay test the produced activin a had the correct secondary structure as the commercial type and was fully active.