4.7 Review

Reconstructing the transcription regulatory network to optimize resource allocation for robust biosynthesis

Journal

TRENDS IN BIOTECHNOLOGY
Volume 40, Issue 6, Pages 735-751

Publisher

CELL PRESS
DOI: 10.1016/j.tibtech.2021.11.002

Keywords

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Funding

  1. National Key R&D Program of China [2019YFA0904104, 2019YFA0906500]
  2. National Nature Science Foundation of China [32000059]
  3. Fundamental Research Funds for the Central Universities

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This review discusses recent engineering strategies targeting the transcription machinery, aiming to reprogram the resource allocation pattern from growth to production. By rearranging the gene regulatory network, a production-oriented phenotype can be constructed, fully harnessing the potential of microbial cell factories.
An ideal microbial cell factory (MCF) should deliver maximal resources to production, which conflicts with the microbe's native growth-oriented resource allocation strategy and can therefore lead to early termination of the high-yield period. Reallocating resources from growth to production has become a critical factor in constructing robust MCFs. Instead of strengthening specific biosynthetic pathways, emerging endeavors are focused on rearranging the gene regulatory network to fundamentally reprogram the resource allocation pattern. Combining this idea with transcriptional regulation within the hierarchical regulatory network, this review discusses recent engineering strategies targeting the transcription machinery, module networks, regulatory edges, and bottom network layer. This global view will help to construct a production-oriented phenotype that fully harnesses the potential of MCFs.

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