A family of radical halogenases for the engineering of amino-acid-based products

Monica E. Neugebauer, Kiera H. Sumida, Jeffrey G. Pelton, Jonathan L. McMurry, Jorge A. Marchand, Michelle C.Y. Chang

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


The integration of synthetic and biological catalysis enables new approaches to the synthesis of small molecules by combining the high selectivity of enzymes with the reaction diversity offered by synthetic chemistry. While organohalogens are valued for their bioactivity and utility as synthetic building blocks, only a handful of enzymes that carry out the regioselective halogenation of unactivated Csp3−H bonds have previously been identified. In this context, we report the structural characterization of BesD, a recently discovered radical halogenase from the FeII/α-ketogluturate-dependent family that chlorinates the free amino acid lysine. We also identify and characterize additional halogenases that produce mono- and dichlorinated, as well as brominated and azidated, amino acids. The substrate selectivity of this new family of radical halogenases takes advantage of the central role of amino acids in metabolism and enables engineering of biosynthetic pathways to afford a wide variety of compound classes, including heterocycles, diamines, α-keto acids and peptides.

Original languageEnglish (US)
Pages (from-to)1009-1016
Number of pages8
JournalNature Chemical Biology
Issue number10
StatePublished - Oct 1 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'A family of radical halogenases for the engineering of amino-acid-based products'. Together they form a unique fingerprint.

Cite this