Preparation and self-cleavage of fusion soluble farnesyl diphosphate synthase in E. coli

Farnesyl diphosphate synthase (FPPS) is a crucial protein in terpenoid production. However, its industrial application is limited owing to its low solubility in Escherichia coli. In this study, we focused on ispA encoding FPPS and designed a fusion expression system to reduce inclusion body (IB) formation. Among the chosen fusion tags, the GB1-domain (GB1) exhibited the highest ability to solubilize the recombinant protein. Increased rare tRNA abundance not only improved the GB1-FPPS yield but also increased its soluble level. A “one-step” method for the acquisition of soluble FPPS was also considered. By combining GB1-FPPS expression and Tobacco Etch Virus protease (TEVp) cleavage in vivo, a controllable GB1-FPPS “self-cleavage” system was constructed. Overall, this study provides an efficient approach for obtaining soluble forms of FPPS, which show great potential for use in the soluble expression of other homologous diphosphate synthase.