US 12,503,706 B2Granted

Microbial cell with improved in vivo conversion of thebaine/oripavine

AssigneeRiver Stone Biotech, LLC

InventorsEsben Halkjaer Hansen, Swee Chuang Lim Hallwyl, Hussam Hassan Nour-Eldin, Zeinu Mussa Belew

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Abstract

A recombinant microbial host cell having improved in vivo conversion of reticuline and derivatives thereof (such as thebaine and/or oripavine) to relevant downstream opioids (such as neopinone, oripavine, northebaine, nororipavine or morphinone) and related compounds (such as heroin, morphine, codeine, thebaine, oripavine, oxycodone, hydrocodone, hydromorphone, oxymorphone, buprenorphine, naltrexone, naloxone or nalbuphine), wherein the microbial (such as fungal) host cell is heterologously expressing at least one functional transporter protein capable of transporting reticuline or a derivative thereof (such as thebaine and/or oripavine) and a heterologously expressed enzyme capable of acting upon reticuline or a derivative thereof. The invention also relates to uses of the microbial host cells and methods of making an opioid compound and/or opioid precursor compound and/or opioid derivative of interest.

Claims14

Dependent claims

A recombinant yeast cell heterologously expressing a transporter protein, wherein the transporter protein:

(i) comprises an amino acid sequence having at least 70% identity with an amino acid sequence selected from the group consisting of SEQ ID NOs:
112, 42, 56, 76, 78, 92, 94, 96, 98, 102, 106, 108, 116, 120, 124, 128, 130, 136, 138, 140, 142, 144, 148, 154, 156, 158, 160, 168, 172, 182, amino acids 1 to 607 of SEQ ID NO:
8, amino acids 1 to 1289 of SEQ ID NO:4, amino acids 1 to 654 of SEQ ID NO:
6, and amino acids 1 to 583 of SEQ ID NO:
10;
and/or
(ii) comprises an amino acid sequence having at least 70% identity with an amino acid sequence selected from the group consisting of SEQ ID NOs:
182, 186, 42, 44, 48, 50, 56, 62, 64, 72, 76, 78, 82, 86, 92, 94, 96, 98, 102, 106, 108, 110, 112, 116, 120, 124, 128, 130, 136, 138, 140, 142, 144, 148, 154, 158, 160, 164, 166, 168, 172, 178, 180, and amino acids 1 to 604 of SEQ ID NO:
31;
and
wherein heterologous expression of the transporter protein improves the recombinant yeast cell uptake of thebaine or oripavine for in vivo conversion.

8 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/285,948Filed 10 Oct 2019
Priority: EP 1820091117 Oct 2018
Published: US 2021/0380995 A19 Dec 2021
Granted: 23 Dec 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification14 codes

C12N 15/81
For fungi: for yeasts
C12N 9/0071
Oxidoreductases: acting on paired donors with incorporation of molecular oxygen
C12P 17/04
Oxygen as only ring hetero atoms: containing a five-membered hetero ring, e.g. griseofulvin , vitamin C
C12P 17/18
Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms: containing at least two hetero rings condensed…