Dissecting the low catalytic capability of flavin-dependent halogenases

Plugging leaks to boost a biocatalyst

26 February 2021

The synthesis of halogenated molecules including many drugs could become much greener, following a biocatalysis study by a team that included Vidyasirimedhi Institute of Science and Technology researchers.

Many molecules, including a third of current drugs, contain a halogen atom — fluorine, chlorine, bromine or iodine — somewhere in their structure. However, the chemical reactions traditionally used to introduce halogen atoms often require toxic reagents and harsh conditions.

Using halogenase enzymes to perform these reactions would be much greener, but currently their use is limited by low catalytic activity.

By studying the reaction mechanism of an enzyme called tryptophan 6-halogenase, the researchers gained new insights into the reaction. In particular, they found that a key reaction intermediate can leak out of the enzyme’s active site, contributing to the enzyme’s low efficiency. 

These discoveries suggest new ways to improve the performance of these enzymes, the team says.

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References

1. Journal of Biological Chemistry 296, 100068 (2021). doi: 10.1074/jbc.RA120.016004