Beyond Cutting: CRISPR-Driven Synthetic Biology Toolkit for Next-Generation Microalgal Metabolic Engineering

Area of Science:

• Synthetic biology
• Microalgal biotechnology
• CRISPR gene editing

Background:

• Microalgae are sustainable cell factories for a circular bioeconomy, but face biological and genetic tool limitations.
• CRISPR-Cas systems initially enabled precise DNA cleavage for gene editing.
• Conventional tools are insufficient for industrial-scale microalgal engineering.

Purpose of the Study:

• To review the evolution and application of CRISPR-derived tools beyond DNA cleavage for microalgal engineering.
• To highlight CRISPR's potential as a versatile synthetic biology tool for microalgae.
• To analyze challenges and future directions for CRISPR in microalgal biomanufacturing.

Main Methods:

• Synthesis of recent advancements in CRISPR-derived technologies (CRISPRa/i, epigenome editors, base/prime editors, multiplexing, logic gates).
• Evaluation of CRISPR tool applications in enhancing microalgal photosynthesis, lipid production, high-value compound synthesis, stress resilience, and carbon utilization.
• Analysis of persistent challenges including species-specific optimization, delivery, stability, scalability, and biosafety.

Main Results:

• CRISPR tools enable tunable gene expression, epigenetic reprogramming, precise editing, metabolic network rewiring, and dynamic control in microalgae.
• Applications include enhanced photosynthesis, increased lipid/biofuel yield, engineered high-value compound pathways, improved stress tolerance, and optimized carbon use.
• Emerging solutions involve AI, automation, and multi-omics integration.

Conclusions:

• CRISPR technology, extending beyond DNA cleavage, offers transformative potential for microalgal engineering.
• Strategic integration of advanced CRISPR tools can create robust, high-productivity microalgal cell factories.
• This unlocks microalgae's promise for next-generation sustainable biomanufacturing.