Microalgal Production of Cannabinoid Precursors via Pathway Assembly
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Solution Overview
Problem
The commercialization of cannabinoid biosynthetic pathway products is hindered by the limitations of plant natural product production, including low accumulation in plants and inefficient extraction methods, and existing microbial platforms struggle to support complex pathway assembly.
Innovation Solution
Genetically engineered microorganisms, such as microalgae and cyanobacteria, are transformed with optimized tetraketide synthase and olivetolic acid cyclase genes to produce olivetolic acid, a precursor in the cannabinoid biosynthetic pathway, using codon-optimized sequences and various constructs to enhance expression and production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If plant-based production methods are used for cannabinoid biosynthetic pathway products, then the products can be obtained through natural processes, but the accumulation is low and extraction methods are time-consuming and inefficient
Solution Approach 1:
The patent copies the cannabinoid biosynthetic pathway genes (TKS and OAC) from Cannabis sativa and expresses them in heterologous microalgal systems. This allows production of olivetolic acid and downstream cannabinoids in microalgae without relying on plant cultivation and extraction, thereby improving productivity and eliminating time-consuming extraction processes
Solution Approach 2:
The patent replaces mechanical extraction methods with biological production. Instead of extracting cannabinoids from plant material through mechanical means, the system uses genetically engineered microalgae to biosynthetically produce the compounds, substituting a biological manufacturing process for a mechanical extraction process
2Productivity
If bacterial or yeast platforms are used for PNP production, then microbial production advantages are gained, but complex PNP pathways cannot be assembled
Solution Approach 1:
The patent changes the host organism parameter from traditional bacteria or yeast to microalgal cells. This parameter change enables the system to assemble complex cannabinoid biosynthetic pathways that involve both polyketide and terpenoid metabolism, which cannot be assembled in bacterial or yeast platforms due to their metabolic limitations
Solution Approach 2:
The patent makes microalgal cells universal hosts capable of performing multiple functions: they can conduct photosynthesis, perform post-translational modifications similar to plants, and assemble complex polyketide-terpenoid hybrid pathways. This multi-functionality allows a single platform to handle the entire cannabinoid biosynthetic pathway
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The genetically engineered microorganisms demonstrate increased production of cannabinoid biosynthetic pathway products, overcoming the limitations of plant-based production and microbial inefficiencies, with enhanced expression and production capabilities.
Implementation Method 1
The genetically engineered microorganisms comprise nucleic acid molecules having nucleic acid sequences encoding cannabinoid biosynthetic pathway enzymes for producing cannabinoid biosynthetic pathway products
Data Source
AI summary
A genetically engineered microorganism for the production of a cannabinoid biosynthetic pathway product is described. The genetically engineered microorganism comprises at least one nucleic acid molecule encoding at least one cannabinoid biosynthetic pathway enzyme. The disclosure also relates to methods for producing a cannabinoid biosynthetic pathway product using a genetically engineered microorganism.