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Chemical modification and protein engineering, by searching for homolog's in hyperthermophiles especially are useful tools for thermo stabilizing proteins, and also for elucidating the mechanism of protein stability that a single or a few amino acid replacement(s) in a protein is/are sufficient to enhance protein thermostability. Many eukaryotes have no homologs protein in the thermophilic organism; protein engineering would be necessary in such cases. Protein engineering may involve directed evolution. The factors affecting the thermal stability of proteins have been identified by comparison of the mesophilic and thermophilic protein belonging to the same protein family. Mainly it concern the tertiary structure of the proteins or their related proteins. One can replace amino acid(s) in a protein by mutagenesis. A promising strategy involves transfer of the identified gene into a thermophile and subsequent growth at higher temperatures. The thermodynamic thermal stability of a protein depends upon the differences in the enthalpy.