Multifactorial level of extremostability of proteins: can they be exploited for protein engineering?

Abstract

Research on extremostable proteins has seen immense growth in the past decade owing to their industrial importance. Basic research of attributes related to extreme-stability requires further exploration. Modern mechanistic approaches to engineer such proteins in vitro will have more impact in industrial biotechnology economy. Developing a priori knowledge about the mechanism behind extreme-stability will nurture better understanding of pathways leading to protein molecular evolution and folding. This review is a vivid compilation about all classes of extremostable proteins and the attributes that lead to myriad of adaptations divulged after an extensive study of 6495 articles belonging to extremostable proteins. Along with detailing on the rationale behind extreme-stability of proteins, emphasis has been put on modern approaches that have been utilized to render proteins extremostable by protein engineering. It was understood that each protein shows different approaches to extreme-stability governed by minute differences in their biophysical properties and the milieu in which they exist. Any general rule has not yet been drawn regarding adaptive mechanisms in extreme environments. This review was further instrumental to understand the drawback of the available 14 stabilizing mutation prediction algorithms. Thus, this review lays the foundation to further explore the biophysical pleiotropy of extreme-stable proteins to deduce a global prediction model for predicting the effect of mutations on protein stability.

Deciphering the rationale behind specific codon usage pattern in extremophiles

“…The GC-content variations in all the classes of extremophilic genomes has been deduced by Chakravorty et al . 28 . The study indicates, in spite of the variation observed in each extremophilic class the basis of extreme-stability selection based only on GC-content could be ambiguous.…”

Structure and function of the Ts2631 endolysin of Thermus scotoductus phage vB_Tsc2631 with unique N-terminal extension used for peptidoglycan binding

“…Endolysins also can kill susceptible bacteria when applied exogenously as recombinant proteins 2 . The features of endolysins desired for their function as potential novel antimicrobial agents are their high stability and resistance to proteolysis and chemical denaturation 3,4 . As these physical properties are common among enzymes of thermophilic microorganisms, we focused our research on lytic enzymes encoded by bacteriophages thriving in extreme thermophilic environments.…”

Recent Development of Extremophilic Bacteria and Their Application in Biorefinery

“…In order to resist the protein unfolding caused by high temperature, thermophilic bacteria have developed special hydrogen bonds that can interact with hydrophobicity. Meanwhile, thermophilic bacterial enzymes are rich in salt bridges and/or extra disulfide bridges to make its structure more stable (Chakravorty et al, 2017). In addition, other thermo-resistance factors, including structural compactness, oligomerization, glycosylation, and hydrophobic interactions between subunits, are crucial for stability (Chakravorty et al, 2017).…”

“…Meanwhile, thermophilic bacterial enzymes are rich in salt bridges and/or extra disulfide bridges to make its structure more stable (Chakravorty et al, 2017). In addition, other thermo-resistance factors, including structural compactness, oligomerization, glycosylation, and hydrophobic interactions between subunits, are crucial for stability (Chakravorty et al, 2017). Synthetic biology, including site-directed mutagenesis and directed evolution of enzymes, has been used to improve the thermal stability of target proteins/enzymes, which is essential for their application in bioenergy industry (Adesioye et al, 2018).…”