Dynamic and tunable metabolite control for robust minimal-equipment assessment of serum zinc

Nat Commun. 2019 Dec 4;10(1):5514. doi: 10.1038/s41467-019-13454-1.

Abstract

Bacterial biosensors can enable programmable, selective chemical production, but difficulties incorporating metabolic pathways into complex sensor circuits have limited their development and applications. Here we overcome these challenges and present the development of fast-responding, tunable sensor cells that produce different pigmented metabolites based on extracellular concentrations of zinc (a critical micronutrient). We create a library of dual-input synthetic promoters that decouple cell growth from zinc-specific metabolite production, enabling visible cell coloration within 4 h. Using additional transcriptional and metabolic control methods, we shift the response thresholds by an order of magnitude to measure clinically relevant zinc concentrations. The resulting sensor cells report zinc concentrations in individual donor serum samples; we demonstrate that they can provide results in a minimal-equipment fashion, serving as the basis for a field-deployable assay for zinc deficiency. The presented advances are likely generalizable to the creation of other types of sensors and diagnostics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biosensing Techniques / instrumentation*
  • Biosensing Techniques / methods
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Metabolic Networks and Pathways*
  • Mutation
  • Spectrometry, Fluorescence
  • Zinc / analysis*
  • Zinc / blood

Substances

  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • Zur protein, E coli
  • Green Fluorescent Proteins
  • Zinc