Multimodal Microorganism Development: Integrating Top-Down Biological Engineering with Bottom-Up Rational Design. Issue 3 (March 2020)

• Record Type: Journal Article
• Authors: Dahabieh, Matthew S.; Thevelein, Johan M.; Gibson, Brian
• Is Part Of: Trends in biotechnology. Volume 38:Issue 3(2020)
• Page Start: 241
• Page End: 253
• Publication Date: 2020-03
• Subjects: biotechnology -- bioeconomy -- synthetic biology -- microbial cell factory -- biological engineering -- rational design; Biotechnology -- Periodicals; Biochemical engineering -- Periodicals; Genetic engineering -- Periodicals; Industrial microbiology -- Periodicals; 660.605
• DOI: 10.1016/j.tibtech.2019.09.006
• Languages: English
• ISSNs: 0167-7799

Abstract

Abstract : Biological engineering has unprecedented potential to solve society's most pressing challenges. Engineering approaches must consider complex technical, economic, and social factors. This requires methods that confer gene/pathway-level functionality and organism-level robustness in rapid and cost-effective ways. This article compares foundational engineering approaches – bottom-up, gene-targeted engineering, and top-down, whole-genome engineering – and identifies significant complementarity between them. Cases drawn from engineering Saccharomyces cerevisiae exemplify the synergy of a combined approach. Indeed, multimodal engineering streamlines strain development by leveraging the complementarity of whole-genome and gene-targeted engineering to overcome the gap in design knowledge that restricts rational design. As biological engineers target more complex systems, this dual-track approach is poised to become an increasingly important tool to realize the promise of synthetic biology. Highlights: Engineered microorganisms are key enablers of the bioeconomy across diverse applications such as fermentation, bioenergy, bioremediation, and biopharmaceuticals. Engineered microorganisms must satisfy real-world, industrial performance requirements – that are often difficult to account for at laboratory scale – to be industrially useful and economically viable. Whole-genome engineering methods using phenotype-based screening/selection are ideally suited for the improvement of complex, multigenic phenotypes. Gene-targeted engineering methods using precision genome editing are ideally suited for constructing pathways and improving traits when sufficient genotype–phenotype mapping information is available. Multimodal strain development leverages the complementarity of whole-genome and gene-targeted engineering to streamline strain development by circumventing incomplete design knowledge and unresolved biological complexity.