Artemisinic Acid Bio-Production Pathway Engineering Service

Artemisinic Acid is the crucial biosynthetic precursor for Artemisinin, the world's leading antimalarial drug. Current supply methods face major instability: plant extraction is greatly affected by climate, agricultural variability, and geopolitical factors , leading to volatile prices. Early synthetic biology attempts also struggle with low yeast expression yield , hindering cost-effective scaling.

CD Biosynsis offers a targeted metabolic engineering solution to establish a stable and high-flux microbial production platform. Our core strategy involves the modification of the mevalonate (MEV) pathway in Saccharomyces cerevisiae to significantly boost the supply of the precursor, farnesyl pyrophosphate ( FPP ). This is coupled with the overexpression and balancing of the key heterologous enzymes, Amorpha-4,11-diene Synthase ( ADS ) and Cytochrome P450 ( CYP71AV1 ) . This integrated approach is designed to explore more efficient and reliable production of Artemisinic Acid, aiming to stabilize the global supply chain for this vital medicine.

Pain Points

Achieving stable and high-volume production of Artemisinic Acid is hampered by these technical challenges:

• Supply Instability: Reliance on Artemisia annua (sweet wormwood) for production means the supply chain is highly vulnerable to weather, pests, and political changes , causing price volatility.
• Precursor Bottleneck: The native MEV pathway in yeast is tightly regulated, leading to a low intracellular concentration of FPP , the essential precursor for Artemisinic Acid synthesis.
• Heterologous Enzyme Efficiency: The key plant enzymes ( ADS and CYP71AV1 ) often display suboptimal activity and poor metabolic coupling when expressed in the yeast host.
• Cofactor Limitation: The P450 step ( CYP71AV1 ) is highly dependent on NADPH , and the host's cofactor regeneration capacity can become a rate-limiting factor.

A sustainable solution requires enhancing the precursor supply chain within the cell and optimizing the terminal catalytic steps.

Solutions

CD Biosynsis utilizes advanced synthetic biology and enzyme engineering to address the production bottlenecks:

Modification of the Mevalonate (MEV) Pathway

           

We employ gene editing to upregulate key rate-limiting enzymes in the MEV pathway (e.g., HMG-CoA reductase) to dramatically enhance the supply of FPP precursor.

Overexpression and Balancing of ADS and CYP71AV1

The heterologous ADS and CYP71AV1 genes are co-expressed and their ratios are balanced using promoter engineering to ensure optimal pathway flux and minimize intermediate buildup.

Redox ( NADPH ) Optimization

We modify the host's central metabolism to enhance the regeneration of NADPH , the necessary cofactor for the P450-mediated CYP71AV1 oxidation step.

Subcellular Localization (ER Targeting)

We use protein targeting signals to localize CYP71AV1 and its reductase partner to the endoplasmic reticulum ( ER ) , which aims to improve enzyme coupling and stability.

This systematic approach is focused on establishing a robust and high-flux sesquiterpenoid biosynthesis platform in yeast.

Advantages

Our Artemisinic Acid engineering service is committed to exploring the following production benefits:

Supply Chain Stability

Microbial production offers an industrialized, climate-independent route , aiming to stabilize the global supply of this critical medicine precursor.

Enhanced Precursor Flux

MEV pathway modification is designed to provide a significantly larger and more stable pool of FPP , essential for sesquiterpene synthesis.

Optimized Enzyme Performance

Targeted enzyme balancing and subcellular localization are focused on maximizing the efficiency of the heterologous plant pathway in yeast.

Reduced Downstream Costs

The fermentation process produces a cleaner product stream than plant extraction, potentially leading to simplified and lower-cost purification . (Image of Cost Reduction Icon)

Robust Yeast Host

Saccharomyces cerevisiae is a well-established industrial chassis, supporting high-density fermentation and scalability for pharmaceutical production.

We provide a biosynthetic platform aimed at overcoming the global supply challenges of Artemisinic Acid.

Process

Our Artemisinic Acid strain engineering service follows a standardized, investigative research workflow:

• MEV Pathway Optimization: Use gene expression analysis and FBA to identify bottlenecks. Up/downregulate key native MEV enzymes to redirect carbon flow toward FPP .
• Heterologous Pathway Construction: Integrate ADS and CYP71AV1 and its reductase partner into the yeast genome, using strong, balanced promoters for co-expression.
• Subcellular and Redox Engineering: Introduce ER targeting sequences to CYP71AV1 and modify the NADPH regeneration pathway to support the P450 reaction.
• Metabolic Byproduct Suppression: Target native pathways that compete for FPP (e.g., squalene synthesis) for downregulation or knockout .
• Fermentation Performance Validation: Test the final engineered strain in high-density fed-batch fermentation, measuring the final titer, yield, and purity .
• Result Report Output: Compile a comprehensive Experimental Report detailing genetic maps, enzyme activity data, fermentation kinetics, and purification feasibility assessment , supporting technology transfer.

Technical communication is maintained throughout the process, focusing on timely feedback regarding precursor supply and terminal enzyme activity.

Explore the potential for a stable, bio-based Artemisinic Acid supply. CD Biosynsis provides customized strain engineering solutions:

• Detailed FPP Flux and Enzyme Activity Analysis Report , illustrating the success of MEV pathway and heterologous enzyme optimization.
• Consultation on fermentation strategies designed to maximize the NADPH supply during the production phase.
• Experimental reports include complete raw data on titer, purity, and long-term strain stability , essential for industrial and regulatory documentation.