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Tyrosine hydroxylase variants and methods of use thereof

Patent ·
OSTI ID:1600224

The present disclosure provides a variant tyrosine hydroxylase that provides for increased production of L-DOPA in a host cell that expresses the tyrosine hydroxylase. The present disclosure provides nucleic acids encoding the variant tyrosine hydroxylase, and host cells genetically modified with the nucleic acids. The present disclosure provides methods of making L-DOPA in a host cell. The present disclosure provides methods of making a benzylisoquinoline alkaloid (BIA), or a BIA precursor. The present disclosure provides methods of detecting L-DOPA level in a cell. The present disclosure provides methods of identifying tyrosine hydroxylase variants that provide for increased L-DOPA production; and methods of identifying gene products that provide for increased tyrosine production.

Research Organization:
Univ. of California, Oakland, CA (United States); Valorbec S.E.C., Montreal, QC (Canada)
Sponsoring Organization:
USDOE
DOE Contract Number:
SC0008084
Assignee:
The Regents of the University of California (Oakland, CA); Valorbec S.E.C. (Montreal, CA)
Patent Number(s):
10,457,918
Application Number:
15/507,711
OSTI ID:
1600224
Country of Publication:
United States
Language:
English

References (17)

A microbial biomanufacturing platform for natural and semisynthetic opioids journal August 2014
An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose journal May 2015
Wound Induced Tanscriptional Regulation of Benzylisoquinoline Pathway and Characterization of Wound Inducible PsWRKY Transcription Factor from Papaver somniferum journal January 2013
Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae journal February 2014
Tyrosine Hydroxylation in Betalain Pigment Biosynthesis Is Performed by Cytochrome P450 Enzymes in Beets (Beta vulgaris) journal February 2016
Microbial production of plant benzylisoquinoline alkaloids journal May 2008
Benzylisoquinoline Alkaloid Metabolism: A Century of Discovery and a Brave New World journal March 2013
Characterization and Functional Identification of a Novel Plant 4,5-Extradiol Dioxygenase Involved in Betalain Pigment Biosynthesis in Portulaca grandiflora journal January 2004
Bioproduction of a betalain color palette in Saccharomyces cerevisiae journal January 2018
Betalain production is possible in anthocyanin-producing plant species given the presence of DOPA-dioxygenase and L-DOPA journal March 2012
Bench-top fermentative production of plant benzylisoquinoline alkaloids using a bacterial platform journal January 2012
The beet R locus encodes a new cytochrome P450 required for red betalain production journal June 2012
Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae journal August 2008
Genetic engineering of yellow betalain pigments beyond the species barrier journal June 2013
Effects of mutations in tyrosine hydroxylase associated with progressive dystonia on the activity and stability of the protein journal October 2004
Detection of DOPA 4,5-Dioxygenase (DOD) Activity Using Recombinant Protein Prepared from Escherichia coli Cells Harboring cDNA Encoding DOD from Mirabilis jalapa journal April 2009
A bacterial platform for fermentative production of plant alkaloids journal May 2011

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