Department of Molecular Biology and Genetics, Faculty of Science, Karadeniz Technical University, Trabzon, Turkey.
Chem Biodivers. 2024 Jan;21(1):e202301255. doi: 10.1002/cbdv.202301255. Epub 2023 Dec 4.
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.
Klotho 是一种具有多种功能的人类蛋白，与长寿和健康有关。循环系统中α-Klotho（α-KL）的缺乏与预期寿命缩短有关，许多疾病如慢性肾脏病、动脉粥样硬化、不孕、皮肤萎缩、肺气肿和骨质疏松症都与之相关。过去二十年来，Klotho 蛋白对难治性癌症的拮抗作用也有充分的记录。此外，最近的发现还阐明了可溶性 Klotho 在认知发育、氧化应激、细胞凋亡和神经退行性疾病中的重要性。低成本和可持续生产α Klotho 蛋白对于其在对抗不同疾病中的广泛应用非常重要。在这里，我们报告了在模式微藻莱茵衣藻中异源、功能和细胞外生产小鼠α-KL（mα-KL）蛋白。mα-KL 分泌到细胞外环境中促进了下游过程，并保证了低成本和高滴度的纯化。此外，还在大鼠 AR42J 胰腺肿瘤上检查和验证了重组 mα-KL 的抗癌效率。基于微藻的光合、低成本和可扩展的 mα-KL 生产可用于开发各种化妆品、药品和保健品，所有这些都旨在服务于健康和幸福。
