Host cells and methods for oxidizing aromatic amino acids
The present invention provides for a method of producing an oxidation product of an aromatic amino acid in a genetically modified host cell. The method comprises culturing the genetically modified host cell under a suitable condition such that the culturing results in the genetically modified host cell producing oxidation product of an aromatic amino acid. The host cell comprises an enzyme capable of catalyzing the oxidation of aromatic amino acid. In some embodiments, the host cell is capable of biosynthesizing BH4 or MH4 from GTP.
1. A genetically modified host cell capable of producing one or more oxidation products of a tyrosine, comprising or is capable of expressing: (a) a tyrosine hydroxylase (TH), (b) pterin-4-alpha-carbinolamine dehydratase (PCD), and (c) dihydropteridine reductase (DHPR); wherein the host cell is capable of expressing L-DOPA decarboxylase (DDC), monoamine oxidase (MAO), and alcohol dehydrogenase (ADH), and the host cell has a native phenylacetaldehyde dehydrogenase, wherein the phenylacetaldehyde dehydrogenase enzyme is truncated or knocked out.
2. The host cell of claim 1 , wherein the TH is mouse TH.
3. The host cell of claim 1 , wherein the DDC is pig DDC.
4. The host cell of claim 1 , wherein the MAO is Micrococcus luteus MAO.
5. The host cell of claim 1 , wherein the gene encoding the native phenylacetaldehyde dehydrogenase enzyme is feaB.