Specialized pro-resolving mediators: Biosynthetic pathways, biocatalytic synthesis, and applications

Area of Science:

• Biochemistry
• Molecular Biology
• Biotechnology

Background:

• Specialized pro-resolving mediators (SPMs) are endogenous lipid mediators crucial for resolving inflammation and infection.
• Derived from polyunsaturated fatty acids, SPMs include lipoxins, resolvins, protectins, and maresins.
• Their potent bioactivities drive interest in food, cosmetic, and therapeutic applications, necessitating high-concentration production.

Purpose of the Study:

• To provide a comprehensive review of SPM nomenclature, classification, biological functions, and biosynthetic pathways.
• To highlight recent advances in the biocatalytic synthesis of SPMs.
• To discuss strategies for enhancing SPM production through enzyme discovery, engineering, and optimization.

Main Methods:

• Review of literature on SPM biosynthesis and biocatalytic production.
• Examination of enzymatic pathways involving lipoxygenases (LOXs), cyclooxygenases, and cytochrome P450s.
• Analysis of microbial biocatalysis, including recombinant cell expression and enzyme engineering.

Main Results:

• Biocatalytic synthesis of SPMs has been significantly advanced by microbial lipoxygenases, achieving gram-per-liter yields.
• Recombinant microbial cells expressing LOXs are effective for efficient SPM production.
• Computational and AI-driven approaches show promise for discovering and engineering high-efficiency LOXs.

Conclusions:

• Microbial biocatalysis offers a viable route for efficient, scalable SPM production.
• Further advancements in enzyme discovery, protein engineering, and AI are critical for optimizing SPM synthesis.
• Enhanced SPM production holds significant potential for therapeutic and industrial applications.