Production of zosteric acid and other sulfated phenolic biochemicals in microbial cell factories

Biological production and application of a range of organic compounds is hindered by their limited solubility and toxicity. This work describes a process for functionalization of phenolic compounds that increases solubility and decreases toxicity. We achieve this by screening a wide range of sulfotransferases for their activity towards a range of compounds, including the antioxidant resveratrol. We demonstrate how to engineer cell factories for efficiently creating sulfate esters of phenolic compounds through the use of sulfotransferases and by optimization of sulfate uptake and sulfate nucleotide pathways leading to the 3′-phosphoadenosine 5′-phosphosulfate precursor (PAPS). As an example we produce the antifouling agent zosteric acid, which is the sulfate ester of p -coumaric acid, reaching a titer of 5 g L −1 in fed-batch fermentation. The described approach enables production of sulfate esters that are expected to provide new properties and functionalities to a wide range of application areas. Toxicity and limited solubility inhibits the biological production of many organic compounds. Here the authors metabolically engineer sulfate uptake and activation in order to produce sulfate esters of phenolic compounds, such as zosteric acid, thereby addressing these issues.