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Production of artemisinin by genetically-modified microbes

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Abstract

Artemisinin, an endoperoxidized sesquiterpene originally extracted from the medicinal plant Artemisia annua L., is a potent malaria-killing agent. Due to the urgent demand and short supply of this new antimalarial drug, engineering enhanced production of artemisinin by genetically-modified or transgenic microbes is currently being explored. Cloning and expression of the artemisinin biosynthetic genes in Saccharomyces cerevisiae and Escherichia coli have led to large-scale microbial production of the artemisinin precursors such as amorpha-4,11-diene and artemisinic acid. Although reconstruction of the complete biosynthetic pathway toward artemisinin in transgenic yeast and bacteria has not been achieved, artemisinic acid available from these transgenic microbes facilitates the subsequent partial synthesis of artemisinin by either chemical or biotransformational process, thereby providing an attractive strategy alternative to the direct extraction of artemisinin from A.annua L. In this review, we update the current trends and summarize the future prospects on genetic engineering of the microorganisms capable of accumulating artemisinin precursors through heterologous and functional expression of the artemisinin biosynthetic genes.

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Abbreviations

ACTs:

Artemisinin-based combination therapies

ADS:

Amorpha-4,11-diene synthase

AMO:

Amorpha-4,11-diene oxidase

CPR:

Cytochrome P450 reductase

CYP/P450:

Cytochrome P450 enzymes

CYP71AV1:

Cytochrome P450 monooxygenase

DMAPP:

Dimethylallyl diphosphate

DXP:

1-deoxy-d-xylulose-5-phosphate

DXR:

1-deoxy-d-xylulose-5-phosphate reductoisomerase

DXS:

1-deoxy-d-xylulose-5-phosphate synthase

ECS:

Epi-cedrol synthase

EST:

Expressed sequence tag

FPP:

Farnesyl pyrophosphate

GGPP:

Geranylgeranyl pyrophosphate

GPP:

Geranyl pyrophosphate

HMG-CoA:

3-hydroxy-3-methylglutaryl coenzyme A

IPP:

Isopentenyl diphosphate

MDR:

Multi-drug resistant

MEP:

Methylerythritol phosphate

MVA:

Mevanolate

RT-PCR:

Reverse transcription-polymerase chain reaction

SS:

Squalene synthase

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Acknowledgments

This article was financially supported by the National Science. Foundation of China (NSFC) under the project numbers of 30672614 and 30271591.

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Authors and Affiliations

  1. Laboratory of Biotechnology, Guangzhou University of Chinese Medicine, 12 Airport Road, Guangzhou, 510405, China

    Qingping Zeng

  2. Simplex Biotechnologies, LLC, Clinton, NJ, 08809, USA

    Frank Qiu

  3. Department of Plant and Soil Sciences, The University of Kentucky, Lexington, KY, 40546, USA

    Ling Yuan

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  1. Qingping Zeng
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  2. Frank Qiu
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  3. Ling Yuan
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Correspondence to Qingping Zeng.

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Zeng, Q., Qiu, F. & Yuan, L. Production of artemisinin by genetically-modified microbes. Biotechnol Lett 30, 581–592 (2008). https://doi.org/10.1007/s10529-007-9596-y

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