Spatial engineering for biocatalytic cascade control through biomolecular compartmentalization

Area of Science:

• Synthetic biology
• Biocatalysis
• Metabolic engineering

Background:

• Metabolic flux orchestration requires spatial solutions beyond traditional enzyme engineering.
• Cellular systems face challenges with enzyme dispersion and native pathway priorities.
• In vitro metabolons offer mechanistic insights into enzymatic cascades.

Purpose of the Study:

• To systematically evaluate spatial engineering platforms for biocatalytic process control.
• To establish a framework for understanding spatial control principles in metabolic landscapes.
• To analyze advances in model construction and functionalized applications of spatial engineering.

Main Methods:

• Review of scaffolded compartments (liposomes, DNA origami, polymersomes, bacterial microcompartments).
• Review of scaffoldless assemblies (membraneless organelles, coacervates).
• Critical analysis of recent advances and functional applications.

Main Results:

• Spatial engineering platforms reconfigure metabolic landscapes in cellular and cell-free systems.
• A framework is established for understanding spatial control principles governing pathway efficiency and flux redistribution.
• Current limitations in mechanistic elucidation, dynamic regulation, and cross-system compatibility are assessed.

Conclusions:

• Spatial engineering offers transformative potential for metabolic flux control.
• Future developments focus on multifunctional spatial organization tools and biomimetic platforms.
• Advances in synthetic biology and cellular engineering are projected.