Bacterial metabolic heterogeneity: origins and applications in engineering and infectious disease

• Published in: Current opinion in biotechnology Vol. 64; pp. 183 - 189
• Main Authors: Evans, Trent D, Zhang, Fuzhong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2020
• Subjects: Bacteria - genetics; Cell Division; Communicable Diseases; Humans; Metabolic Engineering
• ISSN: 0958-1669; 1879-0429
• DOI: 10.1016/j.copbio.2020.04.007

[Display omitted] •Molecular noise, feedback, and asymmetric partitioning create metabolic heterogeneity.•Biosensors, mass spectrometry, and Raman spectroscopy enable single cell measurement.•Minimizing heterogeneity improves ensemble yield in engineered production strains.•Metabolic heterogeneity underlies bacterial persistence. Bacteria within an isoclonal population display significant heterogeneity in metabolism, even under tightly controlled environmental conditions. Metabolic heterogeneity enables influential functions not possible or measurable at the ensemble scale. Several molecular and cellular mechanisms are likely to give rise to metabolic heterogeneity including molecular noise in metabolic enzyme expression, positive feedback loops, and asymmetric partitioning of cellular components during cell division. Dissection of the mechanistic origins of metabolic heterogeneity has been enabled by recent developments in single-cell analytical tools. Finally, we provide a discussion of recent studies examining the importance of metabolic heterogeneity in applied settings such as infectious disease and metabolic engineering.