Abstract
<jats:p>The amino acid-to-enzyme, part-to-whole transition leads to the emergence of enzymatic complexity and diversity. The conventional convergent, heuristic enzymology approach typically classifies enzymes into defined catalytic categories for the predictive identification of enzymes through sequence and conformation homology, thus countering the very essence of emergence. The emphasis on inner core conformational domains for catalysis translates to the tightly confined perspective of discrete domain enzymology. Herein, we report a divergent, emergent enzymology approach, disregard of enzyme classification for the expansive identification of enzymes into the hidden, unchartered categories, thus in compliance with the very essence of emergence. The emphasis on inner-to-outer potential conformational domains for catalysis translates to the broadly open perspective of continuum domain enzymology. In particular, herein, with α,β-unsaturated carbonyls, alkene isomerization as one extra catalytic modality has been identified along with the native carbonyl reduction catalytic modality for ketoreductase, with each effected within disjoint conformational domains. Further, the native carbonyl reduction catalytic modality has empowered the achievement of exquisite flip-flop R-enantioselectivity and Senantioselectivity. The mechanistically disjoint divergence of conformational domains and catalytic modalities within a single enzyme architecture, as showcased herein, epitomizes the very essence of emergence and promises an enormous discovery space for enzymatic complexity and diversity.</jats:p>