In situ solid-liquid extraction enhances recovery of taxadiene from engineered Saccharomyces cerevisiae cell factories

Microbial cell factories express diverse heterologous pathways for the production of a wide range valuable natural products. However, recovery and purification such compounds is major bottleneck in commercialization. In this study, novel situ solid phase adsorption strategy was investigated enhanced taxadiene, precursor to blockbuster anticancer drug, paclitaxel, from engineered Saccharomyces cerevisiae. A synthetic adsorbent resin (HP-20) employed efficiently sequester taxadiene as it secreted during growth carefully optimized desorption solvent applied following cultivation maximize both intracellular across scales (2 – 250 mL). Resin concentration found have an impact on cellular growth, with high 12 % (w/v) resulting fragmentation beads, which detrimental growth. The optimal combination elucidated at microscale mL) resulted two-fold improvement titer 61 ± 8 mg/L, compared traditional liquid-liquid extraction approach (dodecane overlay). Taxadiene be distributed evenly between beads biomass. Performance process subsequently through scale-up using controlled mini-bioreactors (250 Here, comparable 76 19 mg/L achieved despite 125-fold volume. This represented 1.4-fold previous mini-bioreactor scale cultivations dodecane overlay approach.