Bacterial Enoyl-Reductases: The Ever-Growing List of Fabs, Their Mechanisms and Inhibition

Fernanda S M Hopf; Candida D Roth; Eduardo V de Souza; Luiza Galina; Alexia M Czeczot; Pablo Machado; Luiz A Basso; Cristiano V Bizarro

doi:10.3389/fmicb.2022.891610

Bacterial Enoyl-Reductases: The Ever-Growing List of Fabs, Their Mechanisms and Inhibition

Front Microbiol. 2022 Jun 16:13:891610. doi: 10.3389/fmicb.2022.891610. eCollection 2022.

Authors

Fernanda S M Hopf^{1

2}, Candida D Roth¹, Eduardo V de Souza^{1

2}, Luiza Galina^{1

3}, Alexia M Czeczot^{1

3}, Pablo Machado^{1

2}, Luiz A Basso^{1

2

3}, Cristiano V Bizarro^{1

2}

Affiliations

¹ Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF) and Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
² Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
³ Programa de Pós-Graduação em Medicina e Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.

Abstract

Enoyl-ACP reductases (ENRs) are enzymes that catalyze the last step of the elongation cycle during fatty acid synthesis. In recent years, new bacterial ENR types were discovered, some of them with structures and mechanisms that differ from the canonical bacterial FabI enzymes. Here, we briefly review the diversity of structural and catalytic properties of the canonical FabI and the new FabK, FabV, FabL, and novel ENRs identified in a soil metagenome study. We also highlight recent efforts to use the newly discovered Fabs as targets for drug development and consider the complex evolutionary history of this diverse set of bacterial ENRs.

Keywords: FabI; FabK; FabL2; FabV; Fabl; drug targets; fatty acid synthesis; kinetic mechanisms.

Publication types

Review