Developing an effective approach for microbial biosynthesis of hydroxyhydroquinone

Hydroxyhydroquinone (HHQ) is an aromatic triol with important biological activities and values. In this work, we achieved de novo HHQ bioproduction using glucose as the substrate. First, we established a cultivation method to address the issue of HHQ degradation in an aqueous solution. Second, an artificial biosynthesis pathway was constituted in E. coli to enable the conversion of glucose to HHQ via 4-hydroxybenzoate. Moreover, microbial co-culture engineering techniques were utilized to modularize the biosynthesis pathway and improve the HHQ production to 64 mg/L within 48 h. To our knowledge, this is the first report of heterologous biosynthesis of HHQ using a microbial host. The findings of this work lay a solid foundation for future efforts in microbial bioproduction of HHQ and related biochemicals.