Microbial approach for the production of 5-hydroxytryptophan
AssigneeUniversity of Georgia Research Foundation, Inc.
InventorsYajun Yan, Yuheng Lin
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Abstract
5-hydroxytryptophan (5-HTP), a precursor of serotonin, is produced in a microbial host cell. A modified bacterial phenylalanine 4-hydroxylase (P4H) catalyzes the tryptophan 5-hydroxylation reaction. Optionally the host cell includes a cofactor regeneration mechanism, allowing continuous production of 5-HTP without supplementation of exogenous cofactors.
Claims21
A genetically engineered bacterial cell comprising a modified bacterial phenylalanine-4-hydroxylase (P4H) that catalyzes the 5-hydroxylation of tryptophan in the presence of a tetrahydromonapterin (MH4) cofactor, wherein the modified P4H comprises a P4H from Xanthomonas campestris having an amino acid mutation at any one, any two, or all three of amino acid positions 98, 179, and 231 of SEQ ID NO:
- 1, or a modified P4H from Pseudomonas or Ralstonia, selected from the group consisting of:
- a P4H from P. aeruginosa comprising an amino acid mutation at any one, any two, or all three of amino acid positions 84, 162, and 213 of SEQ ID NO:
- 2, a P4H from P. putida having an amino acid mutation at any one, any two, or all three of amino acid positions 84, 162, and 213 of SEQ ID NO:
- 3, a P4H from P. fluorescence comprising an amino acid mutation at any one, any two, or all three of amino acid positions 84, 162, and 213 of SEQ ID NO:
- 4, or a P4H from R. eutropha H16 comprising an amino acid mutation at any one, any two, or all three of amino acid positions 113, 192, and 244 of SEQ ID NO:
- 5.
Dependencies are inferred from the claim text.