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Chemical Biology

A supplement providing a snapshot of the latest developments in chemical biology



New antibiotics from chlorinated natural products


07 February 2006

Understanding the enzymatic chlorination of aromatic and aliphatic biomolecules could lead to new antibiotics says a microbiologist from Ireland.

"Manipulation of biosynthetic gene clusters of antibiotic-producing microorganisms to include halogenase genes offers potential for generating new antibiotic compounds"
- Cormac Murphy
Recently discovered classes of halogenases are now known to be responsible for chlorination in biological systems. Cormac Murphy from the University College Dublin has highlighted these new families of halogenases and their mechanisms of action.

Some chlorine-containing natural products have enhanced antibiotic properties, said Murphy. With more information about the mechanism of enzymatic chlorination, it may be possible to prepare new antibiotic molecules which would otherwise be costly to synthesise using standard chemical reactions. This would involve including halogenase genes in the biosynthetic make-up of antibiotic-producing microorganisms.

One type of halogenase that accounts for the regiospecific addition of chlorine to aromatic compounds is FADH2-dependent. This type of enzyme requires FADH2, a reduced form of flavin adenine dinucleotide (FAD), oxygen and chloride for successful biotransformation. Other families of halogenating enzymes are non-heme FeII alpha-ketoglutarate- and O2-dependent halogenases which have been shown to chlorinate saturated aliphatic compounds.

New antibiotics from chlorinated natural products

Knowledge of the enzymatic chlorination mechanism could widen the scope for the biosynthetic reactions in the biotechnology industry. 'Manipulation of biosynthetic gene clusters of antibiotic-producing microorganisms to include halogenase genes offers potential for generating new antibiotic compounds,' said Murphy.

Alison Stoddart

References

C D Murphy, Natural Product Reports, 2006 (DOI: 10.1039/b516588c)