Constructs and Methods for Biosynthesis of Gastrodin

{
  "publication_number": "US2026103688A1",
  "country": "US",
  "kind": "A1",
  "title": "Constructs and Methods for Biosynthesis of Gastrodin",
  "abstract": "Provided herein are, in various embodiments, host cells, methods, and pharmaceutical compositions including gastrodin, wherein said gastrodin is produced by a transgenic plant or plant cell, fungal cell, yeast cell, insect cell, or bacterial cell. In certain embodiments, the disclosure provides for methods and compositions for the production of gastrodin. In still further embodiments, the disclosure provides for enhanced cells and methods of producing gastrodin.",
  "claims": [
    "1. A host cell comprising a transgene encoding a heterologous uridine 5′-diphospho-glucosyltransferase (UGT) operably linked to a promoter, wherein the heterologous UGT comprises an amino acid sequence comprising SEQ ID NO: 2. 2 - 30. (canceled) 31. The host cell of claim 1, wherein the host cell is a plant cell, a fungal cell, a yeast cell, an insect cell, or a bacterial cell. 32. The host cell of claim 1, wherein the heterologous UGT is codon-optimized for expression in the host cell. 33 - 58. (canceled) 59. A method of producing gastrodin in a host cell, the method comprising culturing the host cell in cell culture medium comprising 4-hydroxybenzyl alcohol, wherein the host cell expresses a transgene that encodes a heterologous uridine 5′-diphospho-glucosyltransferase (UGT) operably linked to a promoter, wherein the heterologous UGT comprises an amino acid sequence comprising SEQ ID NO: 2. 60 - 88. (canceled) 89. The method of claim 59, wherein the host cell is a plant cell, a fungal cell, a yeast cell, an insect cell, or a bacterial cell. 90. The method of claim 59, wherein the heterologous UGT is codon-optimized for expression in the host cell. 91 - 116. (canceled) 117. The method of claim 59, wherein the cell culture medium further comprises glucose. 118. The method of claim 59, further comprising making the host cell, the method comprising introducing a vector into the host cell, the vector comprising a nucleic acid encoding the heterologous uridine 5′-diphospho-glucosyltransferase (UGT) operably linked to the promoter. 119. The method of claim 59, wherein the gastrodin is extracted using maceration, percolation, decoction, reflux extraction, soxhlet extraction, pressurized liquid extraction, supercritical fluid extraction, ultrasound assisted extraction, pulsed electric field extraction, enzyme assisted extraction, hydro distillation, steam distillation, or any combination thereof. 120. The method of claim 59, wherein the concentration of gastrodin within the cell culture medium after 24 h incubation is at least about 4 mM, 6 mM, or 8 mM. 121. The method of claim 59, wherein the concentration of 4-hydroxybenzyl alcohol within the cell culture medium after 24 hr incubation is not greater than 2 mM, 1.5 mM, or 1 mM. 122. A vector comprising a nucleic acid encoding a uridine 5′-diphospho-glucosyltransferase (UGT) for converting 4-hydroxybenzyl alcohol into gastrodin, wherein the uridine 5′-diphospho-glucosyltransferase (UGT) comprises SEQ ID NO: 2. 123. The vector of claim 122, wherein the nucleic acid encoding the uridine 5′-diphospho-glucosyltransferase (UGT) for converting 4-hydroxybenzyl alcohol into gastrodin has at least about 95% nucleotide sequence identity to SEQ ID NO: 1. 124 - 186. (canceled) 187. A method of making a transgenic host cell, the method comprising introducing a vector into a host cell, the vector comprising a nucleic acid encoding a heterologous uridine 5′-diphospho-glucosyltransferase (UGT) operably linked to a promoter, wherein the heterologous UGT comprises an amino acid sequence comprising SEQ ID NO: 2. 188 - 215. (canceled) 216. The method of claim 187, wherein the host cell is a plant cell, a fungal cell, a yeast cell, an insect cell, or a bacterial cell. 217. The method of claim 187, wherein the heterologous UGT is codon-optimized for expression in the host cell. 218 - 244. (canceled)"
  ],
  "description_excerpt": "Gastrodin is a natural product with a range of bioactivities, including neuroprotective, analgesic, and anti-inflammatory effects in both humans and model organisms. Gastrodin is produced by the plant Gastrodia elata, which is also known as Tian Ma in traditional Chinese medicine. Gastrodin is one of the main bioactive components of Gastrodia plant extract. Gastrodin shows efficacy in several pain models and presents itself as a potential treatment for chronic, neuropathic, and chemotherapy-induced pain, both as a single treatment as in combination with other therapeutics.\n\nTo achieve the final conversion of 4-hydroxybenzyl alcohol into gastrodin, which requires a glycosyltransferase (UGT) enzyme that utilizes UDP-glucose as a sugar donor. Several enzymes have been described as gastrodin synthases, including UGT73B6 and AsUGT, and have been engineered into heterologous organisms for the production of gastrodin. (CN113755354A; herein incorporated by reference in its entirety).\n\nHowever, efficient biosynthesis of gastrodin in such heterologous organisms is dependent on the successful transformation of multiple enzymes involved in the glucose to gastrodin biosynthetic pathway. Such processes are cost and time inefficient and result in poor yields. Accordingly, there exists a need for constructs and methods for efficient biosynthesis of gastrodin.",
  "cpc": [
    "C12N 9/1051",
    "C12N 15/66",
    "C12N 2800/22",
    "C12P 19/18",
    "C12P 19/44",
    "C12Y 204/01017"
  ],
  "assignees": [
    "Recombia Biosciences Inc"
  ],
  "inventors": [
    "Michelle GOETTGE",
    "Christopher VICKERY",
    "Jing-Ke WENG"
  ],
  "filing_date": "2023-11-17",
  "publication_date": "2026-04-16",
  "priority_date": "2022-11-17",
  "application_number": "US-202319126747-A",
  "cited_by_count": 0
}