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

13 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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