Mapping CCRs onto a simple classification of “risk factors” immanent in the chemistry of the catalyzed reaction (e.g., a chemically reactive substrate or product or a radical mechanism) is informative low CCRs are consistently linked to risk factors ( Figure 1). (5) Such great variation invites exploration of mechanisms that explain it, i.e., why some enzymes work little before replacement while others work much. The first CCR values to be calculated─for primary metabolic enzymes from the bacterium Lactococcus lactis, yeast, and Arabidopsis─range from 10 7.

These capabilities would be practically useful in enzyme redesign and improvement of in-use stability and could change our thinking about which enzymes die young in vivo, and why. Fortunately, advances in proteomics, metabolomics, cheminformatics, comparative genomics, and structural biochemistry now empower a systematic, data-driven approach for identifying, predicting, and validating instances of active-site damage and its repair. Unfortunately, the data needed to design and execute such improvements are lacking: there are too few measurements of in vivo life span, and existing information about the extent, nature, and mechanisms of active-site damage and repair during normal enzyme operation is too scarce, anecdotal, and speculative to act on. Enzyme life span might also be improved by engineering systems that repair otherwise fatal active-site damage, of which a handful are known and more are inferred to exist.

Analysis also implies that many enzymes are moderately deficient in that their active-site regions are not naturally as hardened against such collateral damage as they could be, leaving room for improvement by rational design or directed evolution.

Analysis of life spans, i.e., lifetime totals of catalytic turnovers, suggests that nonsurvivable collateral chemical damage from the very reactions that enzymes catalyze is a common but underdiagnosed cause of enzyme death.

7 days to die repair