Methods of improving production of morphinan alkaloids and derivatives
AssigneeAntheia, Inc.
InventorsChristina D. SMOLKE, Catherine THODLEY, KRISTY M. HAWKINS, Kenneth TAKEOKA, Douglas HANSEN
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Abstract
Methods and engineered cells are provided for increasing activity of a norcoclaurine synthase in a microbial cell. The method comprises, within the engineered microbial cell, contacting an engineered norcoclaurine synthase with a substrate, wherein contacting the substrate with the engineered norcoclaurine synthase increases conversion, within the engineered microbial cell, in comparison to a non-engineered norcoclaurine synthase.
Claims10
A method of producing a benzylisoquinoline alkaloid (BIA) product in an engineered host cell the method comprising:
- (a) expressing an engineered norcoclaurine synthase in the engineered host cell;
- (b) contacting the engineered norcoclaurine synthase with a BIA-precursor substrate;
- and
- (c) producing the BIA product within the host cell;
- wherein the engineered norcoclaurine synthase comprises an N-terminal truncation and/or one or more amino acid mutations compared to a non-engineered wild-type norcoclaurine synthase, and has increased condensation activity compared to a non-engineered norcoclaurine synthase;
- and
- wherein the engineered host cell produces more BIA product than a non-engineered host cell.
An engineered host cell that produces a benzylisoquinoline alkaloid (BIA) product, the engineered host cell comprising:
- (i) one or more engineered biosynthetic enzymes that reduces accumulation of one or more byproducts that inhibits the production of the BIA product;
- and/or
- (ii) an inactivation of one or more genes that results in the reduction of accumulation of one or more byproduct that inhibits the production of the BIA product.
Dependencies are inferred from the claim text.