Fungal immunoregulatory proteins (FIP) are effective small molecule proteins with broad-spectrum immunomodulatory and anti-cancer activities and can be potential agents for the development of clinical drugs and health food additives.… Click to show full abstract
Fungal immunoregulatory proteins (FIP) are effective small molecule proteins with broad-spectrum immunomodulatory and anti-cancer activities and can be potential agents for the development of clinical drugs and health food additives. In this study, a new member of FIP named FIP-bbo was obtained through Botryobasidium botryosum genome mining. FIP-bbo has the typical characteristics of FIP but is genetically distant from other FIPs. Recombinant FIP-bbo (rFIP-bbo) was produced in an optimized E. coli expression system, and the pure protein was isolated using a Ni-NTA column. Antineoplastic experiments suggested that FIP-bbo is similar to LZ-8 in inhibiting various cancer cells (Hela, Spac-1, and A549) at lower concentrations, but it is not as potent as LZ-8. The molecular mechanism by which FIP-bbo, FIP-fve, and LZ-8 are cytotoxic to cancer cells has been discussed based on molecular dynamics simulation. Point mutations that may improve the thermal stability of FIP-fve and FIP-bbo were predicted. These results not only present a new candidate protein for the development of anticancer adjuvants, but also provide an approach for designing FIPs with high anticancer activity.
               
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