Resveratrol Bioproduction Engineering Service

Resveratrol is a high-value polyphenol used extensively in cosmetics and supplements for its powerful antioxidant and anti-aging properties. Industrial production has traditionally relied on natural plant extraction (e.g., from Japanese knotweed), which results in Low yield and high cost and suffers from variability and environmental impact. Chemical synthesis is complex , yields mixed and often less active isomers (cis/trans), and is environmentally unfriendly . These issues necessitate a stable, high-yield biosynthetic route. The primary biosynthetic challenge is the Insufficient supply of the limiting precursor Malonyl-CoA in the host cell, which is essential for the Resveratrol pathway but is rapidly consumed by native competing pathways.

CD Biosynsis offers a comprehensive synthetic biology and metabolic engineering solution, typically using engineered yeast (S. cerevisiae) or bacteria (E. coli) as hosts. To establish the Resveratrol pathway, we Introduce plant genes into the host, specifically the Phenylpropanoid Pathway genes like 4-Coumarate-CoA Ligase (4CL) and Stilbene Synthase (STS) , which are necessary for converting p-coumaric acid (or tyrosine) into Resveratrol. To overcome the limiting precursor supply, we Overexpress key enzymes like Acetyl-CoA Carboxylase (ACC) to efficiently convert Acetyl-CoA into the required Malonyl-CoA, significantly boosting Resveratrol flux. Finally, to maximize carbon efficiency and purity, we Block competing pathways that synthesize fatty acids or flavonoids , preventing Malonyl-CoA from being diverted and ensuring high Resveratrol yield and high purity of the active trans-Resveratrol isomer.

Pain Points

Developing a cost-effective, high-quality Resveratrol product faces these key challenges:

• Low Yield and High Cost from Natural Extraction: Plant sources provide low concentrations of Resveratrol (e.g., Japanese knotweed), necessitating massive harvesting and complex solvent extraction, resulting in high production costs and environmental burden.
• Complex Chemical Synthesis: Chemical routes are often multi-step, generate mixed isomers (cis-Resveratrol is less active), require high energy, and use hazardous chemicals, making the process environmentally unfriendly .
• Limiting Precursor Supply: The Resveratrol pathway consumes one unit of p-coumaroyl-CoA and three units of Malonyl-CoA. The Insufficient supply of Malonyl-CoA is the main bottleneck, as this precursor is highly volatile and quickly diverted into fatty acid synthesis.
• Pathway Competition: Upstream Phenylpropanoid intermediates (e.g., p-coumaroyl-CoA) are often siphoned into competing flavonoid pathways in yeast or other plant pathway genes introduced into the host.

A successful solution must ensure robust Malonyl-CoA supply and eliminate product competition.

Solutions

CD Biosynsis utilizes advanced metabolic engineering and synthetic biology to optimize Resveratrol production:

Introduce Plant Genes (4CL, STS) into Engineered Hosts

           

We integrate and optimize the 4CL and STS genes from high-activity sources (e.g., Vitis vinifera) to establish the Resveratrol biosynthesis route in the host.

Overexpress Acetyl-CoA Carboxylase (ACC) to Boost Malonyl-CoA Supply

We highly overexpress ACC, the rate-limiting enzyme converting Acetyl-CoA to Malonyl-CoA, resolving the Insufficient supply of Malonyl-CoA bottleneck.

Block Competing Pathways (Fatty Acids, Flavonoids)

We use gene knockouts (e.g., FAS genes, CHS genes) to prevent the diversion of Malonyl-CoA and p-coumaroyl-CoA, maximizing flux to Resveratrol.

Subcellular Compartmentalization and Scaffolding

We use protein scaffolds to physically link 4CL and STS, improving the channeling of intermediates and overall conversion efficiency.

This integrated approach ensures high supply of both precursors and directs the flow towards high-purity Resveratrol product.

Advantages

Our Resveratrol engineering service is dedicated to pursuing the following production goals:

High Titer and Yield

ACC overexpression and pathway blocking eliminate bottlenecks and competition, resulting in significantly higher yields than plant extraction or chemical synthesis.

High Trans-Isomer Purity

Enzymatic synthesis using STS ensures the preferential and highly selective production of the active trans-Resveratrol isomer , avoiding the mixed isomers from chemical routes.

Cost-Effective and Sustainable Production Icon

Microbial fermentation using glucose as a carbon source is more cost-effective and environmentally friendly than complex plant extraction or chemical synthesis. [Image of Cost Reduction Icon]

Consistent Supply Chain Icon

Production is independent of climate, harvesting seasons, and geographical location, providing a reliable source.

Tunable Pathway Icon

The biosynthetic pathway can be tuned to produce specific Resveratrol derivatives (e.g., piceid) for targeted applications.

We provide a superior and sustainable manufacturing platform for trans-Resveratrol.

Process

Our Resveratrol strain engineering service follows a rigorous, multi-stage research workflow:

• Pathway Construction: Design and assemble the heterologous 4CL and STS genes into the host (e.g., S. cerevisiae or E. coli) genome or plasmid.
• Malonyl-CoA Boosting: Overexpress the key enzyme Acetyl-CoA Carboxylase (ACC) using a strong, constitutive promoter to maximize Malonyl-CoA supply.
• Competing Pathway Blockade: Knockout genes responsible for fatty acid synthesis (e.g., FAS genes in yeast) and flavonoid synthesis to funnel precursors.
• Scaffolding Optimization: Introduce synthetic protein scaffolds to colocalize 4CL and STS enzymes, improving metabolic channeling efficiency.
• Titer and Purity Validation: Validate the engineered strain in fed-batch culture, measuring the final Resveratrol titer (g/L) and the trans/cis isomer ratio (HPLC).
• Result Report Output: Compile a detailed Experimental Report including gene modification data, ACC expression levels, and final Resveratrol volumetric titer and purity metrics , essential for commercial feasibility.

Technical communication is maintained throughout the process, focusing on timely feedback regarding yield and product quality attributes.

Explore the potential for a high-titer, high-purity Resveratrol supply. CD Biosynsis provides customized strain and process engineering solutions:

• Detailed Malonyl-CoA Intracellular Concentration Report , demonstrating the effect of ACC overexpression.
• Consultation on optimized fermentation conditions to support maximal trans-Resveratrol stability and production.
• Experimental reports include complete raw data on Resveratrol titer, yield, and final isomer purity , crucial for cosmetic and supplement manufacturing.