IP Library Granted Patent US 11,408,014
Granted Patent B2
US 11,408,014 · App. 17/071,376 · Granted Aug 9, 2022

Mutant thioesterases

Inventors: Brian F. Pfleger (Madison, WI); Nestor Hernandez-Lozada (Jena, DE); Rung-Yi Lai (Changhua, TW)
Assignee: WISCONSIN ALUMNI RESEARCH FOUNDATION
C12P7/6409C12N9/16C12N15/52C12N15/70C12Y301/02
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Quick Facts
Patent No.
US 11,408,014
App. No.
17/071,376
Granted
Aug 9, 2022
Kind
B2
Abstract

Mutant thioesterases having enhanced medium chain substrate activity, polynucleotides encoding and configured to express the mutant thioesterases in a transformed host cell, host cells transformed to contain the polynucleotides, and methods of using same.

Claims (49)

1. An unnatural, mutated protein comprising an amino acid sequence at least 80% identical to SEQ ID NO:4, wherein:

the amino acid sequence comprises:

a serine at a position corresponding to position 59 of SEQ ID NO:4; and

an arginine at a position corresponding to position 296 of SEQ ID NO:4; and

the protein exhibits thioesterase activity.

2. An unnatural, mutated protein comprising an amino acid sequence at least 85% identical to SEQ ID NO:4, wherein:

the amino acid sequence comprises:

a residue other than alanine at a position corresponding to position 59 of SEQ ID NO:4; and

a residue other than lysine at a position corresponding to position 296 of SEQ ID NO:4; and

the protein exhibits thioesterase activity.

3. The protein of claim 2 , wherein the amino acid sequence comprises one or more of:

a serine, cysteine, threonine, asparagine, tyrosine, or glutamine at the position corresponding to position 59 of SEQ ID NO:4; and

an arginine, lysine, or histidine at the position corresponding to position 296 of SEQ ID NO:4.

4. The protein of claim 2 , wherein the amino acid sequence comprises one or more of:

a serine at the position corresponding to position 59 of SEQ ID NO:4; and

an arginine at the position corresponding to position 296 of SEQ ID NO:4.

5. The protein of claim 2 , wherein the amino acid sequence is at least 90% identical to SEQ ID NO:4.

6. The protein of claim 5 , wherein the amino acid sequence comprises one or more of:

a serine, cysteine, threonine, asparagine, tyrosine, or glutamine at the position corresponding to position 59 of SEQ ID NO:4; and

an arginine, lysine, or histidine at the position corresponding to position 296 of SEQ ID NO:4.

7. The protein of claim 5 , wherein the amino acid sequence comprises one or more of:

a serine at the position corresponding to position 59 of SEQ ID NO:4; and

an arginine at the position corresponding to position 296 of SEQ ID NO:4.

8. The protein of claim 2 , wherein the amino acid sequence is at least 95% identical to SEQ ID NO:4.

9. The protein of claim 8 , wherein the amino acid sequence comprises one or more of:

a serine, cysteine, threonine, asparagine, tyrosine, or glutamine at the position corresponding to position 59 of SEQ ID NO:4; and

an arginine, lysine, or histidine at the position corresponding to position 296 of SEQ ID NO:4.

10. The protein of claim 8 , wherein the amino acid sequence comprises one or more of:

a serine at the position corresponding to position 59 of SEQ ID NO:4; and

an arginine at the position corresponding to position 296 of SEQ ID NO:4.

11. The protein of claim 8 , wherein the amino acid sequence comprises:

a serine, cysteine, threonine, asparagine, tyrosine, or glutamine at the position corresponding to position 59 of SEQ ID NO:4; and

an arginine, lysine, or histidine at the position corresponding to position 296 of SEQ ID NO:4.

12. The protein of claim 8 , wherein the amino acid sequence comprises:

a serine at the position corresponding to position 59 of SEQ ID NO:4; and

an arginine at the position corresponding to position 296 of SEQ ID NO:4.

13. A method of producing a fatty acid derivative comprising contacting the unnatural, mutated protein of claim 2 with an acyl-acyl carrier protein substrate or an acyl-coenzyme A substrate under conditions that permit production of the fatty acid derivative.

14. The method of claim 13 , wherein the fatty acid derivative comprises a C8 fatty acid derivative.

15. The method of claim 14 , wherein the C8 fatty acid derivative comprises octanoic acid.

16. The method of claim 13 , wherein the amino acid sequence is at least 95% identical to SEQ ID NO:4.

17. The method of claim 16 , wherein the amino acid sequence comprises:

a serine at the position corresponding to position 59 of SEQ ID NO:4; and

an arginine at the position corresponding to position 296 of SEQ ID NO:4.

18. The method of claim 14 , wherein the amino acid sequence is at least 95% identical to SEQ ID NO:4 and comprises:

a serine at the position corresponding to position 59 of SEQ ID NO:4; and

an arginine at the position corresponding to position 296 of SEQ ID NO:4.

19. The method of claim 15 , wherein the amino acid sequence is at least 95% identical to SEQ ID NO:4 and comprises:

a serine at the position corresponding to position 59 of SEQ ID NO:4; and

an arginine at the position corresponding to position 296 of SEQ ID NO:4.

Assignments (3)
CONFIRMATORY LICENSE Recorded May 23, 2023
From: WISCONSIN ALUMNI RESEARCH FOUNDATION
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 063730/0198 →
CONFIRMATORY LICENSE Recorded Jan 19, 2021
From: UNIVERSITY OF WISCONSIN, MADISON
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 055027/0216 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 16, 2020
From: PFLEGER, BRIAN; HERNANDEZ LOZADA, NESTOR; LAI, RUNG-YI
To: WISCONSIN ALUMNI RESEARCH FOUNDATION
Reel/Frame 054078/0066 →
Continuity (3)
Continuation 16357635 · Mar 19, 2019
Provisional Application 62644954 · Mar 19, 2018
Related Publication 20210040516A1 · Feb 11, 2021