Tools for developing tolerance to toxic chemicals in microbial systems and perspectives on moving the field forward and into the industrial setting

•This review covers recent methods for strain development.•New techniques of discovery enabled by the advent of high throughput technologies.•Rational design builds on existing knowledge with fined tuned analysis techniques.•Perspectives on the challenges and approaches for moving the field forward.

Industrial fermentation imposes environmental challenges for production hosts, therefore robustness in the presence of inhibitory conditions is a necessary trait for biocatalysts. Unfortunately, due to the complex nature of tolerance phenotypes, the genetic determinants associated with tolerance to inhibitory conditions are generally not known, hindering the rational engineering of more robust biocatalysts. Recent technological advances have allowed for the rapid characterization of these complex phenotypes, and hold promise for guiding inverse engineering of tolerance from first principles. Here we review current developments of methods used to uncover the genetic determinants associated with industrially relevant phenotypes and the incorporation of new tools in inverse strain engineering efforts.