Application of artificial scaffold systems in microbial metabolic engineering

In nature, metabolic pathways are often organized into complex structures such as multienzyme complexes, enzyme molecular scaffolds, or reaction microcompartments. These structures help facilitate multi-step metabolic reactions. However, engineered metabolic pathways in microbial cell factories do not possess inherent metabolic regulatory mechanisms, which can result in metabolic imbalance. Taking inspiration from nature, scientists have successfully developed synthetic scaffolds to enhance the performance of engineered metabolic pathways in microbial cell factories. By recruiting enzymes, synthetic scaffolds facilitate the formation of multi-enzyme complexes, leading to the modulation of enzyme spatial distribution, increased enzyme activity, and a reduction in the loss of intermediate products and the toxicity associated with harmful intermediates within cells. In recent years, scaffolds based on proteins, nucleic acids, and various organelles have been developed and employed to facilitate multiple metabolic pathways. Despite varying degrees of success, synthetic scaffolds still encounter numerous challenges. The objective of this review is to provide a comprehensive introduction to these synthetic scaffolds and discuss their latest research advancements and challenges.