River Stone Biotech LLC

Other

Philipp Friedrich Berninger

Esben Halkjaer Hansen

Franziska Grassinger

Markus Schwab

Jon Richard Heal

Joseph Michael Sheridan

Fanny Delgrange

Christophe Folly

Thomas Oestergaard Tange

Curt Aimé Friis Nielsen

Fanny Delegrange

Federico Brianza

Laura Tatjer Recorda

Johannes Haerle

Jens Houghton-larsen

Robert Charles Allan

Jørgen Hansen

Nora Weber

Sumire Honda Malca

Davide Antonio Ravasio

Samantha Jessica Capewell

Angela Manuela Ribeiro De Carvalho

Rubini Maya Kannangara

Ludivine Labagnere

Laura Occhipinti

Anaelle Hatsch

Julien Denis Vivian De Block

Esben Halkjær Hansen

Laura Tatjer RecordÁ

ÂNgela Manuela Ribeiro De Carvalho

The invention relates to norcoclaurine synthases and substrate binding sites having one or more site-specific mutation which increase the activity, when compared to the wild type synthase, of the condensation of 4-HPAA and dopamine to (S)-norcoclaurine and/or 3,4-DhPAA and dopamine to (S)-norlaudanosoline. The inventors both identified specific mutations corresponding to at position 73, 75, 77, 82, 99, 114, 141, 142, 147, 152, 174 and/or 178 in the count according to SEQ ID No: 1, and sites corresponding to the binding domains defined in SEQ ID NO: 4 and 5, where the mutated increase of the activity may be positioned within these norcoclaurine synthases. These domains are conserved regions.

Norcoclaurine synthases with increased activity

Recombinant microorganisms, plants, and plant cells are disclosed that have been engineered to have reduced levels or activity of one or more alcohol dehydrogenases or aldehyde reductases thereby increasing the production of benzylisoquinoline alkaloids and/or benzylisoquinoline alkaloid precursors.

Increased biosynthesis of benzylisoquinoline alkaloids and benzylisoquinoline alkaloid precursors in a recombinant host cell

The invention relates to recombinant host cells that expresses one or more genes encoding a cytochrome P450 enzyme capable of N-demethylating and/O-demethylating reticuline and/or derivatives thereof, and also methods of producing a N-demethylated and/or O-demethylated reticuline and/or derivatives thereof, comprising cultivating the recombinant host of the invention in a culture medium under conditions in which the one or more genes encoding the cytochrome P450 enzymes is/are expressed. The reticuline and derivatives thereof are useful for providing access to naturally unavailable and chemically difficult-to-produce starting materials for opioids.

Demethylation of reticuline and derivatives thereof with fungal cytochrome P450

The invention relates to recombinant microorganisms and methods of producing citronellal, citronellol, citronellic acid, and/or citronellal/citronellol pathway intermediates and precursors.

Production of citronellal and citronellol in recombinant hosts

Growing community of inventors

Basel, Switzerland

Philipp Friedrich Berninger