Khou et al., (2015) Distributing a metabolic pathway among a microbial consortium enhances production of natural products
The aim of the group of Stephanopoulos is to reconstruct a heterologous pathway for a paclitaxel precursor in a microbial partnership.
Therefore, one microbe (E. coli) is engineered to synthesize a metabolic intermediate (taxadiene) which is functionalized by another microbe (S. cerevisiae) producing an activated form of a precursors of the anti-cancer drug paclitaxel. Neither E. coli nor S. cerevisiae can produce the paclitaxel precursor itself. To overcome an inhibition of E. coli by the ethanol S. cerevisiae produced while growing on glucose, a mutualistic interaction between the two microorganisms was created. The co-culture carbon source was switched from glucose to xylose which was used by E. coli and metabolized to acetate which further served as carbon source for S. cerevisiae. By increasing the initial inoculum of yeast and periodically feeding additional xylose, ammonium, and phosphorus, a limitation of nutrients as well as an accumulation of acetate could be eliminated. The taxadiene oxygenation efficiency by S. cerevisiae was further improved by exchanging the TEF promoter by a UAS-GPD promoter.
Relevance of the article:
High relevance: The titers of isoprenoids produced with the methods described above are higher than reported previously. Furthermore, the strategies are widely applicable: the researchers used a co-cultivation of the previously described organisms to produce different oxygenated isoprenoids like Nootkatone and Ferruginol.
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