Production of aromatics in Saccharomyces cerevisiae—A feasibility study

► Theoretical yields for p-hydroxy benzoic acid and p-amino benzoic acid are established in Saccharomyces cerevisiae, Escherichia coli and Pseudomonas putida. ► Toxicity of p-hydroxy benzoic acid and p-amino benzoic acid to S. cerevisiae is quantified. ► Base level production of p-hydroxy benzoic acid and p-amino benzoic acid in S. cerevisiae is achieved through metabolic engineering. Aromatics are amongst the most important bulk feedstocks for the chemical industry, however, no viable bioprocess exists today and production is still dependent on petro-chemistry. In this article the production of aromatic precursors such as p-hydroxybenzoic acid (PHBA) and p-amino benzoic acid (PABA) in Saccharomyces cerevisiae was evaluated using metabolic network analysis. Theoretical mass yields for PHBA and for PABA obtained by metabolic network analysis were 0.58 and 0.53ggglucose−1, respectively. A major setback for microbial production of aromatics is the high toxicity of the products. Therefore, PHBA and PABA toxicity was evaluated in S. cerevisiae. Minimal inhibitory concentrations of 38.3gL−1 for PHBA and 0.62gL−1 for PABA were observed. However, PABA toxicity could be alleviated in adaptation experiments. Finally, metabolic engineering was used to create proof of principle first generation strains of S. cerevisiae. Overall accumulation of 650μM PHBA and 250μM PABA could be achieved.