Method for increasing the yield of oxidosqualene, triterpenes and/or triterpenoids and host cell therefore
AssigneesFraunhofer-Gesellschaft zur Foerderung der angewandten Forschung e.V., Westfaelische Wilhelms-Universitaet Muenster
InventorsChristian Schulze Gronover, Lowis Gerrit Boje Mueller, Nicole Van Deenen, Jan Niklas Broeker
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Abstract
The present invention relates to a method of increasing the yield of at least one of oxidosqualene, triterpenes and/or triterpenoids in a specifically engineered host cell and a respective host cell as well as to the use of said host cell for manufacturing the at least one of oxidosqualene, triterpenes and/or triterpenoids.
Claims19
A recombinant host cell for manufacturing one or more of oxidosqualene(s), triterpene(s) and triterpenoid(s), wherein the host cell is engineered to overexpress a 3-hydroxy-3-methylglutaryl-coenzyme A reductase comprising the amino acid sequence as shown in SEQ ID NO:
- 1, and to overexpress a protein comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs:
- 2, 3, 4, 5, 6, 7 and 8, and wherein the one or more of oxidosqualene(s), triterpene(s) and triterpenoid(s) is/are selected from the group consisting of an oxidosqualene, a sterol, a pentacyclic triterpene, an acylated triterpene, β-amyrin, α-amyrin, taraxasterol, a triterpene acetate, an acylated triterpene, taraxerol, taraxerone, α-amyrone, β-amyrone, taraxasterone, friedelin, betulin, betulinic acid, cholesterol, ergosterol, lanosterol, a glucocorticoid, a mineralocorticoid, an estrogen, a gestagen, a cardenolide, a bufadienolide, and a steroidalkaloid,
- wherein the host cell comprises a knock out of at least one locus selected from the group consisting of ROX1 (SEQ ID NO:
- 25), BTS1 (SEQ ID NO:
- 54), YPL062W (SEQ ID NO:
- 55), DOS2 (SEQ ID NO:
- 56), YER134C (SEQ ID NO:
- 57), VBA5 (SEQ ID NO:
- 58), YNR063W (SEQ ID NO:
- 59), YJL064W (SEQ ID NO:
- 60) and YGR259C (SEQ ID NO:
- 61).
A method of making a recombinant host cell that manufactures one or more of oxidosqualene(s), triterpene(s), and triterpenoid(s), comprising a step of
- engineering a host cell to:
- overexpress a 3-hydroxy-3-methylglutaryl-coenzyme A reductase comprising SEQ ID NO:
- 1,
- overexpress a protein comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs:
- 2, 3, 4, 5, 6, 7, and 8, and
- knock out at least one locus selected from the group consisting of ROX1 of SEQ ID NO:
- 25, BTS1 of SEQ ID NO:
- 54, YPL062W of SEQ ID NO:
- 55, DOS2 of SEQ ID NO:
- 56, YER134C of SEQ ID NO:
- 57, VBA5 of SEQ ID NO:
- 58, YNR063W of SEQ ID NO:
- 59, YJL064W of SEQ ID NO:
- 60 and YGR259C of SEQ ID NO:
- 61, and
- wherein the one or more of oxidosqualene(s), triterpene(s) and triterpenoid(s) is/are selected from the group consisting of an oxidosqualene, a sterol, a pentacyclic triterpene, an acylated triterpene, β-amyrin, α-amyrin, taraxasterol, a triterpene acetate, an acylated triterpene, taraxerol, taraxerone, α-amyrone, β-amyrone, taraxasterone, friedelin, betulin, betulinic acid, cholesterol, ergosterol, lanosterol, a glucocorticoid, a mineralocorticoid, an estrogen, a gestagen, a cardenolide, a bufadienolide, and a steroidalkaloid.
Dependencies are inferred from the claim text.