AI Article Synopsis
- The study emphasizes the importance of overexpressing the DXS enzyme from the MEP pathway and using short-chain prenyltransferase fusions to enhance the production of taxa-4,11-diene, a key precursor for the anti-cancer drug paclitaxel.
- Results indicated that a genetically engineered strain featuring the txs gene, overexpressed MEP pathway genes, and incorporated fusion proteins achieved a record high yield of 390 mg/L of taxa-4,11-diene.
- This achievement marks a thirteen-fold increase compared to previous records in B. subtilis, highlighting the critical role of DXS overexpression and prenyltransferase fusions in improving terpene production.
Article Abstract
This study highlights the significance of overexpressing 1-deoxy-d-xylulose-5-phosphate synthase (DXS) from the MEP (methylerythritol 4-phosphate) pathway, in addition to short-chain prenyltransferase fusions for the improved production of the diterpene, taxa-4,11-diene, the first committed intermediate in the production of anti-cancer drug paclitaxel. The results showed that the strain which has (i) the taxadiene synthase (txs) gene integrated into the genome, (ii) the MEP pathway genes overexpressed, (iii) the fpps-crtE prenyltransferases fusion protein and (iv) additional expression of 1-deoxy-d-xylulose-5-phosphate synthase (DXS), yielded the highest production of taxa-4,11-diene at 390 mg/L (26 mg/L/OD). This represents a thirteen-fold increase compared to the highest reported concentration in B. subtilis. The focus on additional overexpression of DXS and utilizing short-chain prenyltransferase fusions underscores their pivotal role in achieving significant titer improvements in terpene biosynthesis.
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| http://dx.doi.org/10.1016/j.nbt.2024.06.007 | DOI Listing |
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