Exploring alternative routes and strategies for producing aromatic biochemicals

Aromatic compounds represent a diverse and useful class of target bioproducts with a range of applications including as fine and bulk chemicals, as well as molecular building blocks. Although traditionally derived from petroleum feedstocks and/or directly from plant biomass, recent efforts to engineer ‘microbial chemical factories’ for their direct biosynthesis from renewable biomass sugars show promise for improving the renewability and sustainability of the approach. With a vast and comprehensive ‘toolkit’ of enzyme chemistries co-evolved via disparate anabolic, catabolic, and detoxification processes, efficient construction of aromatic biosynthetic pathways is supported by a particularly abundant and natural availability of useful enzyme ‘parts’. Owing to this diversity, it is often possible to conceptualize and ultimately engineer multiple unique enzyme pathways to arrive at the same aromatic product of interest. However, as such alternative routes incorporate different endogenous precursors, enzyme chemistries, cofactors, and intermediates, they often differ with respect to pathway energetics, host compatibility, and, ultimately, achievable production metrics. In this presentation we will provide an overview of our recent efforts related to the conceptualization and engineering of alternative pathways for the production of non-inherent and/or non-natural aromatic biochemicals. Specifically, we will describe efforts related to the engineering of multiple novel pathways in Escherichia coli for the production of phenol and 2-phenylethanol, as well as a modular network of pathways for the production of catechol and muconic acid.