Efflux Pumps and Porins Enhance Bacterial Tolerance to Phenolic Compounds by Inhibiting Hydroxyl Radical Generation

Phenolic compounds are industrially versatile chemicals that have been successfully produced in microbial cell factories. Unfortunately, most phenolic compounds are highly toxic to cells in specific cellular environments or above a particular concentration because they form a complex with iron and promote hydroxyl radical production in Fenton reactions, resulting in the ferroptosis of cells. Here, we demonstrated that overexpression of efflux pumps and porins, including porins LamB and OmpN, and efflux pumps EmrAB, MdtABC, and SrpB, can enhance Escherichia coli phloroglucinol (PG) tolerance by inhibiting the generation of hydroxyl radicals. In addition, LamB and OmpN overexpression improved the bioproduction of PG. Furthermore, efflux pumps and porins can enhance bacterial tolerance to various phenolic compounds, including phenol, catechol, resorcinol, pyrogallol, and 2-naphthol. LamB and MdtABC confer a generalized tolerance to phenols. However, EmrAB, OmpN, and SrpB showed inconsistent effects of bacterial tolerance to different phenolic compounds. Our results will theoretically support the construction of phenolic compound-tolerant bacteria strains, which should be more efficient in the biosynthesis of phenols.