The configuration, composition and aims of the bioprocesses make them unique between each other, even if the target molecule and source of biosynthesis are the same. Many authors categorise bioprocess in two main parts, upstream bioprocess and downstream bioprocess. The upstream bioprocess focuses in how the target molecule is produced or synthesised while the downstream bioprocess focuses on how this molecule is going to be recovered or purified. If we centre our attention on downstream bioprocess integration, we are talking about how to the operation units that conform the downstream bioprocess interact between them in order to have a holistic understanding on how the molecule is being retrieved. After the interactions between the operation units are well known and studied, the integration of the bioprocess can be done by substituting two or more unit operations by one unit capable of achieving the same process aim without losing yield or molecule denaturalisation.
At our research team, we use the bioprocess integration to augment the taxane yields using combined methodologies. These strategies occurs mainly in the production and extraction steps where we are intensifying the bioprocess making two or more processes in one this single step to recover more taxanes.
Currently, we have developed a methodology that uses in situ solid phase adsorption using commercial resin beads (HP-20) from the start of the edited yeast cultivation process. The adsorption of taxanes is achieved by the interaction of the resin beads suspended in the media during the yeast growth. Once the cultivation period is over, we use a membrane-disrupt organic solvent to extract the taxanes from the cells and from the resin beads. This methodology is described in Figure 1.
Figure 1. Heterologous taxadiene biosynthetic pathway in S. cerevisiae engineered strain (LRS5) and concurrent in situ adsorption of the secreted taxadiene to the surface of the HP-20 resin beads. Taxadiene is adsorbed onto the resin surface as it is secreted throughout the cultivation and extracted at the end using an appropriate organic solvent (Santoyo-Garcia et al., 2021).
This methodology has brought important improves in taxadiene yields compared to the traditional dodecane overlay method, depending on the cultivation scale, up to 1.9-fold (Santoyo-Garcia et al., 2021). our research is still going into using different approaches with different resin materials, different organisms and extraction procedures.
Feel free to contact us if you are interested to collaborate in increasing your natural products yields from any microorganisms you are working with.
Santoyo-Garcia, J. H., Walls, L. E., Nowrouzi, B., Ochoa-Villareal, M., Loake, G. J., Dimartino, S., & Rios-Solis, L. (2021). In situ solid-liquid extraction enhances recovery of taxadiene from engineered S . cerevisiae cell factories. BioRxiv, 2021.07.12.452013. https://doi.org/10.1101/2021.07.12.452013