WO2019183193A1 – September 26, 2019 – ENZYMES, CELLS, AND METHODS FOR PRODUCTION OF 3-(4-FARNESYLOXYPHENYL)PROPIONIC ACID

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Inventors :

PHILIPPE, Ryan, Nicholas - c/o Manus Bio, Inc., 1030 Massachusetts Avenue, Cambridge, MA 02138; KUMARAN, Ajikumar, Parayil - c/o Manus Bio, Inc., 1030 Massachusetts Avenue, Cambridge, MA 02138; SANTOS, Christine, Nicole S. - c/o Manus Bio, Inc., 1030 Massachusetts Avenue, Cambridge, MA 02138

Owner :

MANUS BIO, INC.

Application Number :

WOUS19023123

Document Number :

WO2019183193A1

Priority Date :

January 1, 1970

Filing Date :

March 20, 2019

Date of Grant/ Publication :

September 26, 2019

Class :

C12N15 / 74; C12N15 / 70; C12N9 / 10; C12N1 / 21; C12N1 / 19; A61K8 / 97; C12P5 / 00; C12P7 / 52; A61Q19 / 02

Abstract

The present disclosure provides microbial cells and methods of producing FOPPA resulting from unique biosynthetic pathways, including biosynthetic pathways based on the phenylalanine/tyrosine biosynthetic branch and biosynthetic pathways based on bacteria metabolism. In particular, the present invention provides methods of producing FOPPA in microbial cells. These methods provide a low-cost, sustainable, and environmentally friendly source for FOPPA.

Claim(s)

1. A microbial cell producing 3-(4-famesyloxyphenyl)propionic acid (FOPPA), or a derivative thereof, comprising: an enzyme pathway for the synthesis of a first substrate that is selected from famesyl pyrophosphate, famesyl-phosphate, or famesol; an enzyme pathway for the synthesis of a second substrate that is selected from phloretate or an analog thereof, and a transferase enzyme forming FOPPA, or a derivative thereof, from the first substrate and the second substrate.;
36. A method for making FOPPA, or a derivative thereof, comprising: contacting a first substrate and a second substrate with a prenyltransferase to make FOPPA, or a derivative thereof, wherein the first substrate is selected from famesyl pyrophosphate, famesyl-phosphate, or fames ol; wherein the second substrate is selected from phloretate or a precursor or analog thereof, and wherein the prenyltransferase comprises an amino acid sequence selected from Aspergillus terreus aromatic Prenyl Transferase (AtaPT) having an accession number selected fromKP893683, EAU39348, EAU39467, EAU36097, EAU36020, EAU31601, EAU29429, and EAU29303, or a variant thereof, and a transferase enzyme comprising an amino acid sequence selected from SEQ ID NOs: 2 to 22 or a variant thereof.

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