Functional and Extracellular Production and Antitumor Activity of Mouse Alpha Klotho in Model Microalga Chlamydomonas reinhardtii

Abstract

Klotho is a human protein with versatile functions associated with longevity and well‐being. α‐Klotho (α‐KL) deficiency in the circulatory system is associated with reduced life expectancy with numerous disorders such as chronic kidney disease, atherosclerosis, infertility, skin atrophy, emphysema, and osteoporosis. The antagonistic effects of Klotho protein against intractable cancers have also been well documented over the past two decades. In addition, recent findings have also illuminated the importance of soluble Klotho during cognitive development, oxidative stress, cellular apoptosis, and neurodegenerative disorders. The low‐cost and sustainable production of alpha Klotho protein is extremely important for its widespread use against different diseases. Here, we report heterologous, functional, and extracellular production of mouse α‐KL (mα‐KL) protein in model microalga Chlamydomonas reinhardtii. The secretion of mα‐KL into the extracellular environment facilitated downstream processes and warranted low‐cost purification in high‐titer. Furthermore, the anticarcinogenic efficiency of recombinant mα‐KL was examined and validated on Rattus norvegicus AR42J pancreas tumors. Microalgae‐based photosynthetic, low‐cost, and scalable production of mα‐KL could be used to develop a variety of cosmetics, pharmaceuticals, and wellness products, all aimed at serving health and well‐being.