Harnessing Underground Metabolism for Pathway Development

Trends Biotechnol. 2019 Jan;37(1):29-37. doi: 10.1016/j.tibtech.2018.08.001. Epub 2018 Aug 29.


Fermentative production of valuable substances is an economically competitive and ecologically sustainable alternative to chemical synthesis, but it is often hampered by detrimental interactions between the heterologous pathway and the host metabolic network. These interactions are diverse and often not understood. However, the growing knowledge about convergently evolved pathways offers an expansive toolbox to engineer novel, hybrid pathways that could circumvent current problems by recruiting the host 'underground metabolism'. Moreover, considering the debate about genetically modified organisms, harnessing the intrinsic capacity of a cell could be promising for food or feed technologies. This opinion article proposes a ubiquitously applicable and technologically simple approach using metabolic rewiring of reversely engineered hybrid pathways.

Keywords: adaptive laboratory evolution; convergent evolution; enzyme promiscuity; metabolic engineering; pathway evolution; suppressor mutation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biotechnology / methods*
  • Enzymes / genetics*
  • Enzymes / metabolism*
  • Fermentation
  • Metabolic Engineering / methods*
  • Metabolic Networks and Pathways / genetics*


  • Enzymes