A family of radical halogenases for the engineering of amino-acid-based products.
Nat Chem Biol
; 15(10): 1009-1016, 2019 10.
Article
de En
| MEDLINE
| ID: mdl-31548692
ABSTRACT
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 [Formula see text] 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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Streptomyces
/
Protéines bactériennes
/
Ingénierie des protéines
/
Acides aminés
Langue:
En
Journal:
Nat Chem Biol
Sujet du journal:
BIOLOGIA
/
QUIMICA
Année:
2019
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique