Abstract

Demetallation of heme to release iron is a chemical difficult reaction and is highly rare in biochemistry, with apoferritin as the only known enzyme responsible for this process. Here we show the heme degradation enzyme ChuW catalyzes heme demetallation besides its known methyltransferase activity (which converts heme to a ring-open product anaerobilin).

We show the demetallation activity of ChuW is radical SAM-dependent, and likely involves the same set of intermediates involved in the anaerobilin-producing pathway. The ChuW-catalyzed demetallation reaction does not require external reductant, and can occur on several heme analogs with different metal centers. These findings establish a brand-new chemistry in the radical SAM enzymes, highlighting the remarkable catalytic diversity of this superfamily of enzymes.