Enzymatic Modification Of Amino Acids And Their Products

Tech ID: 30533 / UC Case 2020-003-0

Patent Status

Patent Pending

Brief Description

The inventors report the structural characterization of BesD, a recently discovered radical halogenase from the FeII/-ketogluturate family that chlorinates the free amino acid lysine. They also identify and characterize additional halogenases that produce mono- and di-chlorinated 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 biosynthetic pathways to afford a wide variety of compound classes, such as heterocycles, diamines, -keto acids, and peptides. 

Suggested uses

  • Use to produce halogenated (X = Cl, I, Br) and azidated amino acids directly, with downstream conversion through substitution/elimination to other groups like amino, ether, ester, thioether, fluoro, cyano, etc.
  • Use to produce downstream products of amino acids, such as ketoacids, amines, heteroccycles
  • Use to produce modified peptides and proteins for functional modification (addition of polymers, toxins, delivery agents, imaging agents)
  • Use to produce modified peptides and proteins for structional modification (peptide macrocycles, stapled peptides)
  • Use for in vivo tagging applications (Halo tagging)

Advantages

While organohalogens are valued for their bioactivity and utility as synthetic building blocks, only a handful of enzymes that can carry out the regioselective functionalization of unactivated Csp3-H bonds have previously been identified. The integration of synthetic and biological catalysis enables new approaches to the synthesis of small molecule targets by crossing the high selectivity of enzymes with the reaction diversity offered by synthetic chemistry.  The substrate selectivity of this new family of radical halogenases takes advantage of the central role of amino acids in metabolism and enables engineering biosynthetic pathways to afford a wide variety of compound classes, such as heterocycles, diamines, -keto acids, and peptides. 

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Inventors

  • Chang, Michelle C. Y.

Other Information

Keywords

synthetic biology, chemoenzymatic, biotransformation, metabolic engineering

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