Strategies for Improved Docosahexaenoic Acid Synthesis in Microalgae

Area of Science:

• Biotechnology
• Marine Biology
• Nutritional Science

Background:

• Docosahexaenoic acid (DHA), an essential omega-3 fatty acid vital for brain development, is traditionally sourced from fish oil.
• Ethical sourcing of fish oil faces challenges including off-flavors and contamination with persistent organic pollutants.
• Microalgae present a sustainable and viable alternative for DHA production, but cost-effective optimization is key.

Purpose of the Study:

• To systematically review advancements in enhanced DHA production from microalgae over the past decade (2015-2025).
• To explore methods for optimizing DHA yield, focusing on genetic engineering, mutagenesis, and cost-effective fermentation strategies.
• To analyze the molecular mechanisms underlying high-yield DHA production in microalgae.

Main Methods:

• Systematic review of literature from 2015-2025 on microalgal DHA production.
• Analysis of studies employing mutagenomics (e.g., ARTP mutagenesis) for yield enhancement.
• Evaluation of genetic engineering techniques, including gene overexpression and manipulation of metabolic pathways.
• Assessment of fermentation optimization using low-cost carbon and nitrogen sources.
• Integration of transcriptomics and metabolomics data to understand DHA biosynthesis.

Main Results:

• ARTP mutagenesis achieved DHA yields up to 41.4 g/L.
• Genetic engineering, including gene manipulation in carbohydrate and lipid metabolism, yielded up to 51.5 g/L of DHA.
• Low-cost substrates like maize starch hydrolysate and soybean meal hydrolysate improved biomass and DHA yield (20.7 g/L).
• Adaptive laboratory evolution with cane molasses and sucrose dehydrogenase overexpression increased DHA yield by 162.86% (25.26 g/L).
• Transcriptomics revealed upregulated genes in central carbohydrate metabolism, fatty acid synthase (FAS), and polyketide synthase (PKS) pathways, correlating with high NADPH and acetyl-CoA demand.

Conclusions:

• Microalgae are a promising sustainable source for high-yield DHA production.
• Mutagenesis and genetic engineering significantly enhance DHA yields.
• Optimization of fermentation media with cost-effective nutrients is crucial for economic viability.
• Understanding molecular mechanisms through omics approaches aids in further strain improvement for DHA production.