Multicatalytic cooperativity enables divergent photobiocatalytic C-C couplings for scaffold diversification
Most new-to-nature enzymatic reactions have arisen from mechanism-guided design, whereas synthetically useful, yet unanticipated enzymatic reactivity remains difficult to identify. Here we show that systematic interrogation of enzyme-photocatalyst pairings can reveal emergent reactivity inaccessible to either catalyst alone. By evaluating combinations of diverse {gamma}-functionalization…
A novel study has demonstrated that combining enzyme-photocatalyst pairings can lead to the discovery of previously unknown enzymatic reactions. Researchers systematically investigated enzyme-photocatalyst combinations, evaluating diverse {gamma}-functionalization pyridoxal phosphate (PLP) enzymes with a variety of photocatalysts.
This approach revealed emergent reactivity that was inaccessible to either catalyst alone, including a previously unknown migratory {beta}-cross-coupling and a canonical {gamma}-cross-coupling. Building upon these findings, the team employed directed evolution through substrate tunnel engineering to generate an orthogonal set of biocatalysts.
These biocatalysts enabled the selective production of branched or linear non-canonical amino acids, showcasing enhanced pathway and stereochemical control. The study highlights the potential of exploring multicatalytic cooperativity as a complementary method for uncovering valuable and previously unrecognized enzymatic reactivity in synthetic applications.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
