Computer-Assisted Engineering of stable hLIF

Zhishuai Liu,Renpeng Guo, Zheng Liu,Guanyu Qin, Hao Lu, Libang Zhou,Shijie Ding,Guanghong Zhou

Food Bioscience(2024)

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Abstract
Due to their capacity for long-term expansion and differentiation potential, embryonic stem cells (ESC) can be selected as seed cells for generating cultured meat. Leukemia inhibitory factor (LIF) is a pleiotropic cytokine with a wide range of activities, including maintaining ESC in a totipotent state in vitro, which is an essential additive component of the ESC proliferation medium. However, owing to the low thermal stability of wide-type human LIF (hLIF-WT), the cost was increased by repeatedly added and storage loss. Here, we tackle this problem using a computer-assisted protein engineering strategy to create a unique modified hLIF with three mutations displaying unprecedented stability and enhanced biological function. The molecule holds considerable promise for stem cell research and the cultured meat field.
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Key words
Embryonic stem cell,Leukemia inhibitory factor,Computational design,Protein engineering,Protein stability
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