Strain engineering via regulatory noncoding RNAs: not a one-blueprint-fits-all

• Regulatory noncoding RNAs (ncRNAs) are powerful tools in metabolic engineering.
• Adjusting expression of natural ncRNAs allows regulation of multiple pathways.
• Modular designs of synthetic ncRNAs enable efficient, targeted gene regulation.

Increasing demands for efficient, sustainable chemical production continue to motivate engineering of microbial strains. Noncoding RNAs (ncRNAs) represent a class of powerful regulators of cellular processes and are emerging as significant tools for strain engineering, particularly for complex phenotypes. Current strategies include adjusting expression levels of natural ncRNAs and developing synthetic ncRNAs to target specific genes. In this review, we summarize and analyze the effectiveness of the design blueprints for a variety of natural and synthetic ncRNA systems recently reported in the literature to offer a concise and easy to read engineering guide to exploiting trans-regulatory ncRNAs for strain engineering.