A new family of iron-dependent halogenases acts on freestanding substrates.

Regio- and stereospecific incorporation of a halogen atom to an unactivated sp(3) carbon in a freestanding molecule is a challenging transformation that is currently missing in the inventory of enzyme-mediated reactions. Here we report what is to our knowledge the first example of a nonheme iron enzyme (WelO5) in the welwitindolinone biosynthetic pathway that can monochlorinate an aliphatic carbon in 12-epi-fischerindole U and 12-epi-hapalindole C, substrates that are free from peptidyl or acyl carrier protein.