Deciphering Tryptophan Oxygenation: Key Modulators of 2-Oxindole Formation in MarE.

ABSTRACT: MarE, a heme-dependent aromatic oxygenase with a histidyl axial ligation, catalyzes the monooxygenation of β-methyl-l-tryptophan to form a 2-oxindole scaffold central to maremycin biosynthesis. Although structurally similar to tryptophan 2,3-dioxygenase (TDO), which initiates l-tryptophan catabolism via dioxygenation, MarE exhibits distinct reactivity modulated by ascorbate. While ascorbate has no effect on TDO, it promotes selective monooxygenation by MarE. In its absence, MarE favors dioxygenation and formation of pyrroloindoline products, revealing latent catalytic versatility. Active-site loop sequences differ between the two enzymes, SLGGR in MarE versus GTGGS in TDO, prompting loop-swapping experiments to probe structure-function relationships. Substituting GTGGS in TDO to MarE-like

SUBMITTER: Nguyen RC 

PROVIDER: S-EPMC12312684 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature