Tyrosine hydroxylase variants and methods of use thereof

US10457918B2 · kind B2 · utility

Assignees

• The Regents of the University of California · US
• VALORBEC, SEC · CA

Inventors

• Vincent Martin · Montréal, CA
• Lauren Narcross · Montréal, CA
• John E. Dueber · San Francisco, US
• William C. DeLoache · Oakland, US
• Zachary Nicholas Russ · Travilah, US
• P. James Scrivens · Saint-Constant, CA

Key dates

• Filing date: Sep 24, 2015
• Grant date: Oct 29, 2019
• Expiry date: Sep 24, 2035

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Y114/16002
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

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.