Halometabolites are compounds that are commonly found in nature and they ar
e produced by many different organisms. Whereas bromometabolites can mainly
be found in the marine environment, chlorometabolites are predominately pr
oduced by terrestrial organisms; iodo- and fluorocompounds are only produce
d infrequently. The halogen atoms are incorporated into organic compounds b
y enzyme-catalyzed reactions with halide ions as the halogen source. For ov
er 40 years haloperoxidases were thought to be responsible for the incorpor
ation of halogen atoms into organic molecules. However, haloperoxidases lac
k substrate specificity and regioselectivity. and the connection of haloper
oxidases with the in vivo formation of halometabolites has never been demon
strated. Recently, molecular genetic investigations showed that, at least i
n bacteria, a different class of halogenases is involved in halometabolite
formation. These halogenases were found to require FADH(2), which can be pr
oduced from FAD and NADH by unspecific flavin reductases. In addition to FA
DH(2), oxygen and halide ions (chloride and bromide) are necessary for the
halogenation reaction. The FADH(2)-dependent halogenases show substrate spe
cificity and regioselectivity, and their gents have been detected in many h
alometabolite-producing bacteria, suggesting that this type of halogenating
enzymes constitutes the major source for halometabolite formation in bacte
ria and possibly also in other organisms.