The present disclosure provides genetically modified host cells that produce a cannabinoid, a cannabinoid derivative, a cannabinoid precursor, or a cannabinoid precursor derivative. The present disclosure provides methods of synthesizing a cannabinoid, a cannabinoid derivative, a cannabinoid precursor, or a cannabinoid precursor derivative.

This document relates to using bidirectional, multi-enzymatic scaffolds to biosynthesize cannabinoids in recombinant hosts.

The present disclosure provides genetically modified host cells that produce a cannabinoid, a cannabinoid derivative, a cannabinoid precursor, or a cannabinoid precursor derivative. The present disclosure provides methods of synthesizing a cannabinoid, a cannabinoid derivative, a cannabinoid precursor, or a cannabinoid precursor derivative.

A method is provided for biosynthetic production of cannabinoids in microorganisms from a carbon source precursor. This method describes the genetic modifications needed to engineer microorganisms to produce cannabinoids as well as a method for identifying and quantifying cannabinoids from fermentation broth. A system is also provided for tuning the method to produce different cannabinoids of interest by systematically modulating the enzymes encoded by the genetic modifications introduced in the microorganism.

To provide a recombinant cell being an anaerobic archaeon, including a gene encoding isoprene synthase, a gene encoding monoterpene synthase, a gene encoding sesquiterpene synthase, a gene encoding diterpene synthase, a gene encoding squalene synthase, or a gene encoding phytoene synthase as a first foreign gene, wherein the first foreign gene is expressed, and the recombinant cell is capable of producing isoprene or terpene having 10, 15, 20, 30, or 40 carbon atoms.

The present disclosure provides genetically modified host cells that produce a cannabinoid, a cannabinoid derivative, a cannabinoid precursor, or a cannabinoid precursor derivative. The present disclosure provides methods of synthesizing a cannabinoid, a cannabinoid derivative, a cannabinoid precursor, or a cannabinoid precursor derivative.

The present invention provides for a genetically modified host cell capable of producing isopentenol and/or 3-methyl-3-butenol, comprising (a) an increased expression of phosphomevalonate decarboxylase (PMD) (b) an increased expression of a phosphatase capable of converting isopentenol into 3-methyl-3-butenol, (c) optionally the genetically modified host cell does not express, or has a decreased expression of one or more of NudB, phosphomevalonate kinase (PMK), and/or PMD, and (d) optionally one or more further enzymes capable of converting isopentenol and/or 3-methyl-3-butenol into a third compound, such as isoprene.

The invention features compositions and methods for the increased production of mevalonate, isoprene, isoprenoid precursor molecules, and/or isoprenoids in microorganisms via the heterologous expression of the mvaE and mvaS genes from the organisms Listeria grayi DSM 20601, Enterococcus faecium, Enterococcus gallinarum EG2, and Enterococcus casseliflavus.

Described are 3-hydroxyisovalerate (HIV) synthase variants having improved activity in converting acetone and a compound which provides an activated acetyl group into 3-hydroxyisovalerate (HIV). Moreover, described are in particular methods for the production of 3-hydroxyisovalerate and methods for the production of isobutene from acetone utilizing the HIV synthase variants of the present invention.

Geranyl pyrophosphate (GPP) is a key intermediate molecule in the bioproduction of thousands of natural products. Currently, natural products are either cultivated from plants, synthesized via complex chemical synthesis strategies, or through cell-based factories also known as biofoundries. However, in order to replicate the process in a cell free environment, numerous enzymes and cofactors must be utilized making this approach costly and unviable. In order to make this process viable, a new approach was needed that uses fewer enzymes and co-factors. As described herein, the present invention demonstrates that it is possible to create GPP from glycerol through a short and concise biosynthetic pathway outside of the cell.