Multienzyme cascade biotransformation of L-Tyrosine to Danshensu by engineered Escherichia coli

Danshensu (DSS), a water-soluble bioactive compound with significant antioxidant, anti-inflammatory, cardioprotective and neuroprotective properties, is widely utilized in cardiovascular and cerebrovascular disease. In this study, we established a multi-enzyme cascade system in engineered Escherichia coli to synthesize DSS from L-Tyrosine. The initial co-expression of 4-hydroxyphenylacetate 3-monooxygenase (HpaBC), L-amino acid deaminase (aadL), glucose dehydrogenase (gdh) and D-lactate dehydrogenase (ldhD) yielded 5.1 mM DSS. The production of DSS increased to 6.53 mM through optimizing plasmid copy number. After optimizing the conditions, the yield of DSS reached 8.66 mM from strain 6. Finally, whole cell biotransformation using strain 6 in bioreactor yielded 19.47 mM DSS within 32h. These findings provide valuable insights for the scalable biosynthesis of pharmaceutically important compound of DSS from naturally available substrates of L-Tyrosine.