# US 10,370,689 B2 · Production of lysergic acid by genetic modification of a fungus

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- Number: US 10,370,689 B2
- Document ID: US10370689B2
- Status: Granted
- Kind: B2
- Application number: 15/700,598
- Filed: 2017-09-11
- Published: 2017-12-28
- Granted: 2019-08-06
- Earliest claimed: 2014-06-16
- Assignees: West Virginia University
- Applicants: West Virigina University
- Inventors: Daniel G. Panaccione; Sarah L. Robinson
- Web page: https://patentgrep.com/patent/US10370689B2

## CPC

- C12P 17/182: {Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system (alloxazine or isoalloxazine, e.g. riboflavine C12P25/00)}
- C12N 1/14: Fungi (culture of mushrooms A01G18/00; as new plants A01H15/00); Culture media therefor
- C12N 15/52: Genes encoding for enzymes or proenzymes
- C12P: FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {(brewing of beer C12C; producing vinegar C12J; producing specific peptides or proteins C07K; producing enzymes C12N9/00; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; measuring or testing processes involving enzymes or microorganisms C12Q; measuring or testing processes involving nucleic acid amplification reactions C12Q1/6844; fermentation processes to form a food composition, A21 or A23; compounds in general, see the relevant compound class, e.g. C01, C07)}
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention provides a method of producing lysergic acid and other ergot alkaloids by genetic modification of a fungus. A strain of fungus comprising Aspergillus fumigatus (A. fumigatus) or any fungus having a pathway similar to Aspergillus fumigatus and expressing one or more genes of the ergot alkaloid biosynthesis pathway from one or more fungus selected from the group consisting of Epichloë festucae var. lolii×Epichloë typhina isolate Lp1 (E. sp. Lp1); Claviceps species; Claviceps africana (C. africana); Claviceps gigantea (C. gigantea); Epichloë coenophiala and Periglandula species, wherein gene easA or gene easM is inactivated in said A. fumigatus or said fungus having a pathway similar to Aspergillus fumigatus, is provided.

## Claims

### Claim 1

A strain of fungus comprising Aspergillus fumigatus (A. fumigatus) and expressing one or more genes of the ergot alkaloid biosynthesis pathways from Epichloë festucae var. lolii×Epichloë typhina isolate Lp1 (E. sp. Lp1), and optionally one or more fungus selected from the group consisting of:
a. Claviceps species;
b. Claviceps africana (C. africana);
c. Claviceps gigantea (C. gigantean);
d. Periglandula species; and
e. Epichloë coenophiala,
and wherein gene easM is inactivated in A. fumigatus, and wherein one or more genes of the ergot alkaloid biosynthesis is cloA.

### Claim 2

A strain of fungus comprising Aspergillus fumigatus (A. fumigatus) and expressing one or more genes of the ergot alkaloid biosynthesis pathways from Claviceps africana (C. africana), and optionally one or more fungus selected from the group consisting of:
a. Epichloë festucae var. lolii×Epichloë typhina isolate LD1 (E. sp. L 1);
b. Claviceps species;
c. Claviceps gigantea (C. gigantean);
d. Periglandula species; and
e. Epichloë coenophiala,
and wherein gene easM is inactivated in A. fumigatus, and wherein one or more genes of the ergot alkaloid biosynthesis is cloA.

### Claim 3

A strain of fungus comprising Aspergillus fumigatus (A. fumigatus) and expressing one or more genes of the ergot alkaloid biosynthesis pathways from Claviceps gigantea (C. gigantean), and optionally one or more fungus selected from the group consisting of:
a. Epichloë festucae var. lolii×Epichloë typhina isolate Lp1 (E. sp. Lp1);
b. Claviceps species;
c. Claviceps africana (C. africana);
d Periglandula species; and
e. Epichloë coenophiala,
and wherein gene easM is inactivated in said A. fumigatus, and wherein one or more genes of the ergot alkaloid biosynthesis is cloA.

### Claim 4

A strain of fungus comprising SEQ ID NO:7.