Santoyo-Garcia, JH;
Walls, LE;
Nowrouzi, B;
Galindo-Rodriguez, GR;
Ochoa-Villarreal, M;
Loake, GJ;
Dimartino, S;
(2022)
In situ solid-liquid extraction enhances recovery of taxadiene from engineered Saccharomyces cerevisiae cell factories.
Separation and Purification Technology
, 290
, Article 120880. 10.1016/j.seppur.2022.120880.
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In situ solid-liquid extraction enhances recovery of taxadiene from engineered Saccharomyces cerevisiae cell factories.pdf - Accepted Version Download (3MB) | Preview |
Abstract
Microbial cell factories express diverse heterologous pathways for the production of a wide range of valuable natural products. However, the recovery and purification of such compounds is a major bottleneck in commercialization. In this study, a novel in situ solid phase adsorption strategy was investigated for enhanced recovery of taxadiene, a precursor to the blockbuster anticancer drug, paclitaxel, from engineered Saccharomyces cerevisiae. A synthetic adsorbent resin (HP-20) was employed to efficiently sequester taxadiene as it was secreted during growth and a carefully optimized desorption solvent was applied following cultivation to maximize recovery of both secreted and intracellular taxadiene, across a range of scales (2 – 250 mL). Resin concentration was found to have an impact on cellular growth, with the high concentration of 12 % (w/v) resulting in fragmentation of the resin beads, which was detrimental to growth. The optimal resin concentration and desorption solvent combination elucidated at microscale (2 mL) resulted in a two-fold improvement in taxadiene titer to 61 ± 8 mg/L, compared to the traditional liquid-liquid extraction approach (dodecane overlay). Taxadiene was found to be distributed evenly between resin beads and biomass. Performance of the optimal process was subsequently investigated through scale-up using controlled mini-bioreactors (250 mL). Here, a comparable taxadiene titer of 76 ± 19 mg/L was achieved despite a 125-fold scale-up in cultivation volume. This represented a 1.4-fold improvement in taxadiene recovery compared to previous mini-bioreactor scale cultivations using the dodecane overlay extraction approach.
| Type: | Article |
|---|---|
| Title: | In situ solid-liquid extraction enhances recovery of taxadiene from engineered Saccharomyces cerevisiae cell factories |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.seppur.2022.120880 |
| Publisher version: | https://doi.org/10.1016/j.seppur.2022.120880 |
| Language: | English |
| Additional information: | Copyright © 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Taxadiene, In situ solid phase adsorption, Mini-bioreactor, HP-20 resin beads, Saccharomyces cerevisiae |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10183093 |
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