Global Market Demand:

As awareness of health and nutrition grows, DHA (Docosahexaenoic Acid) is widely recognized for its significant benefits to brain development, vision, and cardiovascular health. It is commonly used in functional foods, infant formula, and dietary supplements. However, traditional forms of DHA, such as triglyceride or ethyl ester, have relatively low bioavailability, requiring higher doses to achieve the desired effects [1].

In contrast, DHA-PC (Phosphatidylcholine-bound DHA), a more advanced form of DHA, exhibits distinct physiological advantages and is increasingly gaining market attention. The phospholipid-bound DHA not only shows superior absorption and metabolic efficiency compared to traditional DHA but also demonstrates enhanced targeting of the brain and nervous system.

Advantages of DHA-PC over DHA:

Higher Bioavailability:

Research shows that DHA-PC has significantly higher absorption efficiency compared to DHA triglycerides or ethyl esters. The phospholipid-bound form is more easily absorbed through the intestinal wall and rapidly transported to the brain and nervous tissue [2].

Enhanced Targeting of Brain and Nervous System:

The phospholipid structure of DHA-PC closely resembles brain phospholipids, allowing it to cross the blood-brain barrier more effectively [3]. This makes DHA-PC an ideal form for enhancing brain function and protecting neural health, particularly in infant brain development and in preventing neurodegenerative diseases in the elderly.

Stronger Anti-inflammatory and Cardiovascular Protection:

While DHA itself possesses strong anti-inflammatory and cardiovascular protective effects, studies suggest that DHA-PC is more effective in lowering triglycerides and reducing atherosclerosis [4]. The phospholipid-bound form also improves fat metabolism, further enhancing cardiovascular benefits.

Better Stability and Taste:

Due to its phospholipid structure, DHA-PC is more stable and less prone to oxidation, avoiding the common fishy taste associated with traditional DHA products. This makes DHA-PC a more suitable additive for high-end nutritional and functional food products.

Current Challenges:

Despite its numerous advantages, DHA-PC is mainly sourced from krill oil, which poses environmental sustainability issues, high production costs, and limited supply. Overfishing further strains Antarctic ecosystems. The current extraction process for DHA-PC is complex and not scalable to meet growing market demand.

Given these challenges, developing a sustainable, efficient, and cost-effective method for synthesizing DHA-PC through biomanufacturing is imperative.

Core Objective:

To develop a microbial biomanufacturing platform for DHA-PC synthesis using synthetic biology approaches, offering a sustainable, economical, and efficient alternative to krill oil.

Specific Objectives:

Construct and optimize genetically engineered strains for phospholipid synthesis.

Optimize metabolic pathways and protein expression to achieve high-yield DHA-PC biosynthesis.

Gene Engineering:

Employ synthetic biology to introduce key enzymes (e.g., LACS, LPCAT) involved in phospholipid synthesis into industrial strains such as yeast or E. coli.

Enhance enzyme activity through mutagenesis, improving DHA-PC synthesis efficiency.

Metabolic Flux Optimization:

Use metabolic engineering tools to optimize key pathways, enhancing substrate supply and DHA-PC production efficiency.

Apply flux balance analysis (FBA) models to predict and optimize the effects of genetic regulation on DHA-PC yield.

Technical Outcomes:

Development of a high-efficiency DHA-PC biomanufacturing process.

Docosahexaenoic acid coenzyme A, a key product in the production of DHA-PC, was obtained to verify the feasibility of this phospholipid production method.

Commercial Outcomes:

Provide a low-cost, sustainable production method for DHA-PC, applicable to functional foods, dietary supplements, and pharmaceuticals.

Overcome dependence on krill oil, enabling scalable, cost-effective DHA-PC production.

Market Potential:

There is significant global demand for DHA and phospholipid products, especially in infant, maternal, elderly, and sports nutrition sectors. As a premium nutrient, DHA-PC has vast market potential.

Applications:

strong>Functional Foods: DHA-PC can be added to infant formula and maternal nutrition products to enhance brain and vision development.

Dietary Supplements: DHA-PC can be formulated as a cardiovascular health supplement to lower triglycerides and prevent chronic diseases.

Pharmaceutical Industry: DHA-PC can improve drug targeting and stability, making it useful in cancer treatment and neuroprotection through drug delivery systems.

Technical Advancements:

Further optimize genetically engineered strains and fermentation processes to increase production efficiency and reduce costs.

Explore the biosynthesis of other phospholipids such as EPA-PC (Eicosapentaenoic Acid Phosphatidylcholine).

Industrialization and Collaboration:

Partner with companies in food, supplements, and pharmaceuticals to commercialize the project’s outcomes and enable large-scale production.

Build a complete supply chain from biomanufacturing to end-product delivery.

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• S. C. R. Sherratt, R. A. Juliano, C. Copland, D. L. Bhatt, P. Libby and R. P. Mason, Journal of Lipid Research, 2021, 62, 100106.
• J. Qin, E. Kurt, T. LBassi, L. Sa and D. Xie, Frontiers in Microbiology, DOI:10.3389/fmicb.2023.1280296.