Using structure-function relationships to understand the mechanism of phenazine-mediated extracellular electron transfer in Escherichia coli

Zayn Rhodes; Olja Simoska; Ashwini Dantanarayana; Keith J Stevenson; Shelley D Minteer

doi:10.1016/j.isci.2021.103033

Using structure-function relationships to understand the mechanism of phenazine-mediated extracellular electron transfer in Escherichia coli

iScience. 2021 Aug 25;24(9):103033. doi: 10.1016/j.isci.2021.103033. eCollection 2021 Sep 24.

Authors

Zayn Rhodes¹, Olja Simoska¹, Ashwini Dantanarayana¹, Keith J Stevenson², Shelley D Minteer¹

Affiliations

¹ Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
² Center for Energy Science and Technology, Skolkovo Institute of Science and Technology, Bolshoi Boulevard 30 Bld. 1, Moscow 121205, Russia.

Abstract

Phenazines are redox-active nitrogen-containing heterocyclic compounds that can be produced by either bacteria or synthetic approaches. As an electron shuttles (mediators), phenazines are involved in several biological processes facilitating extracellular electron transfer (EET). Therefore, it is of great importance to understand the structural and electronic properties of phenazines that promote EET in microbial electrochemical systems. Our previous study experimentally investigated a phenazine-based library as an exogenous mediator system to facilitate EET in Escherichia coli. Herein, we combine our experimental data with density functional theory (DFT) calculations and multivariate linear regression modeling to understand the structure-function relationships in phenazine-based mediated EET. These calculations demonstrate that the computed redox properties of phenazines in lipophilic environments (e.g., cell membrane) correlate to experimental mediated current densities. Additional DFT-derived molecular properties were considered to develop a predictive model, which could be used in metabolic engineering approaches to introduce phenazines as endogenous mediators into bacteria.

Keywords: Applied microbiology; Bio-electrochemistry; Chemistry; Computational chemistry; Electrochemistry; Microbiology.