Please use this identifier to cite or link to this item:
https://doi.org/10.3390/molecules22091422
Title: | Multienzyme biosynthesis of dihydroartemisinic acid | Authors: | Chen X. Zhang C. Too H.-P. |
Keywords: | aldehyde dehydrogenase isoenzyme 1 amorpha-4,11-diene artemisinin derivative cytochrome P450 dihydroartemisinic acid fungal protein isoenzyme retinal dehydrogenase sesquiterpene biocatalysis biosynthesis chemistry enzymology genetics growth, development and aging metabolism oxidation reduction reaction Saccharomyces cerevisiae Artemisinins Biocatalysis Biosynthetic Pathways Cytochrome P-450 Enzyme System Fungal Proteins Isoenzymes Oxidation-Reduction Retinal Dehydrogenase Saccharomyces cerevisiae Sesquiterpenes |
Issue Date: | 2017 | Publisher: | MDPI AG | Citation: | Chen X., Zhang C., Too H.-P. (2017). Multienzyme biosynthesis of dihydroartemisinic acid. Molecules 22 (9) : 1422. ScholarBank@NUS Repository. https://doi.org/10.3390/molecules22091422 | Abstract: | One-pot multienzyme biosynthesis is an attractive method for producing complex, chiral bioactive compounds. It is advantageous over step-by-step synthesis, as it simplifies the process, reduces costs and often leads to higher yield due to the synergistic effects of enzymatic reactions. In this study, dihydroartemisinic acid (DHAA) pathway enzymes were overexpressed in Saccharomyces cerevisiae, and whole-cell biotransformation of amorpha-4,11-diene (AD) to DHAA was demonstrated. The first oxidation step by cytochrome P450 (CYP71AV1) is the main rate-limiting step, and a series of N-terminal truncation and transcriptional tuning improved the enzymatic activity. With the co-expression of artemisinic aldehyde dehydrogenase (ALDH1), which recycles NADPH, a significant 8-fold enhancement of DHAA production was observed. Subsequently, abiotic conditions were optimized to further enhance the productivity of the whole-cell biocatalysts. Collectively, approximately 230 mg/L DHAA was produced by the multi-step whole-cell reaction, a ~50% conversion from AD. This study illustrates the feasibility of producing bioactive compounds by in vitro one-pot multienzyme reactions. © 2017 by the authors. | Source Title: | Molecules | URI: | https://scholarbank.nus.edu.sg/handle/10635/175151 | ISSN: | 1420-3049 | DOI: | 10.3390/molecules22091422 |
Appears in Collections: | Staff Publications Elements |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
10_3390_molecules22091422.pdf | 2.46 MB | Adobe PDF | OPEN | None | View/Download |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.