Next Article in Journal
The Effect of Pressure and Solvent on the Supercritical Fluid Chromatography Separation of Tocol Analogs in Palm Oil
Previous Article in Journal
One-Pot Green Regioselesctive Synthesis of γ-Lactones from Epoxides and Ketene Silyl Acetals Using 1,3-Dimethylimidazolium Fluoride as a Recoverable Metal-Free Catalyst
Previous Article in Special Issue
A New Approach to Synthesize of 4-Phenacylideneflavene Derivatives and to Evaluate Their Cytotoxic Effects on HepG2 Cell Line
Article Menu
Issue 9 (September) cover image

Export Article

Open AccessArticle
Molecules 2017, 22(9), 1422; doi:10.3390/molecules22091422

Multienzyme Biosynthesis of Dihydroartemisinic Acid

1
Biotransformation Innovation Platform, Agency for Science Technology and Research, Singapore 138673, Singapore
2
Department of Biochemistry, National University of Singapore, Singapore 117598, Singapore
*
Authors to whom correspondence should be addressed.
Received: 13 August 2017 / Revised: 27 August 2017 / Accepted: 27 August 2017 / Published: 28 August 2017
(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)
View Full-Text   |   Download PDF [2463 KB, uploaded 28 August 2017]   |  

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. View Full-Text
Keywords: whole cell biocatalysis; CYP71AV1; dihydroartemisinic acid whole cell biocatalysis; CYP71AV1; dihydroartemisinic acid
Figures

Figure 1a

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Chen, X.; Zhang, C.; Too, H.-P. Multienzyme Biosynthesis of Dihydroartemisinic Acid. Molecules 2017, 22, 1422.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top