Evolutionary approaches for engineering industrially-relevant phenotypes in bacterial cell factories

Lorena Fernandez-Cabezon, Antonin Cros, Pablo Ivan Nikel*

*Corresponding author for this work

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The bio-based production of added-value compounds (with applications as pharmaceuticals, biofuels, food ingredients, and building blocks) using bacterial platforms is a well-established industrial activity. The design and construction of microbial cell factories (MCFs) with robust and stable industrially-relevant phenotypes, however, remains one of the biggest challenges of contemporary biotechnology. In this review, we discuss traditional and cutting-edge approaches for optimizing the performance of MCFs for industrial bioprocesses, rooted on the engineering principle of natural evolution (i.e. genetic variation and selection). We present state-of-the-art techniques to manipulate and increase genetic variation in bacterial populations and to construct combinatorial libraries of strains, both globally (i.e. genome-level) and locally (i.e. individual genes or pathways, and entire sections and gene clusters of the bacterial genome). Cutting-edge screening and selection technologies applied to isolate MCFs displaying enhanced phenotypes are likewise discussed. We close the review article by presenting future trends in the design and construction of a new generation of MCFs that will contribute to the long-sought-after transformation from a petrochemical industry to a veritable sustainable bio-based industry. This article is protected by copyright. All rights reserved.
Original languageEnglish
Article numbere1800439
JournalBiotechnology Journal
Issue number9
Number of pages17
Publication statusPublished - 2019


  • Adaptive laboratory evolution
  • Combinatorial engineering
  • Industrially-relevant phenotypes
  • Metabolic engineering
  • Synthetic Biology

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