Multimodal Microorganism Development: Integrating Top-Down Biological Engineering with Bottom-Up Rational Design

Matthew S. Dahabieh, Johan M. Thevelein, Brian Gibson (Corresponding Author)

Research output: Contribution to journalReview Articlepeer-review

7 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)241-253
Number of pages13
JournalTrends in Biotechnology
Issue number3
Early online date22 Oct 2019
Publication statusPublished - Mar 2020
MoE publication typeA2 Review article in a scientific journal


  • bioeconomy
  • biological engineering
  • biotechnology
  • microbial cell factory
  • rational design
  • synthetic biology


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