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Review
. 2023 Dec 22:11:1328141.
doi: 10.3389/fbioe.2023.1328141. eCollection 2023.

Application of artificial scaffold systems in microbial metabolic engineering

Nana Liu  1   2 , Wei Dong  2 , Huanming Yang  2 , Jing-Hua Li  1 , Tsan-Yu Chiu  1   2
Affiliations
Review

Application of artificial scaffold systems in microbial metabolic engineering

Nana Liu et al. Front Bioeng Biotechnol. .

Abstract

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.

Keywords: enzyme molecular scaffolds; microbial cell factory; multienzyme complexes; reaction microcompartments; synthetic scaffold.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Protein scaffold; (A) Enzyme complex assembly based on PDZ domain and ligand interaction, adapted from (Gao et al., 2014); (B) Enzyme complex assembly based on mPKSeal strategy, adapted from (Sun et al., 2022).
FIGURE 2
FIGURE 2
DNA scaffold system based on TALE, adapted from (Xie et al., 2019).
FIGURE 3
FIGURE 3
Organelle scaffold; (A) Functional assembly of multienzyme systems on outer membrane vesicles, adapted from (Park et al., 2014); (B) Compartmental assembly of endoplasmic reticulum derived metabolic vesicles, adapted from (Reifenrath et al., 2020).
See this image and copyright information in PMC

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