Jay D. Keasling

Dr. Jay D. Keasling


Research Focus & Metrics

Academic Career Length

38Years (1989-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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13 April 2006 in Nature
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Journal Article
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DRDae-Kyun Ro
Dae-Kyun Ro
EPEric M. Paradise
Eric M. Paradise
MOMario Ouellet
Mario Ouellet
KFKarl J. Fisher
Karl J. Fisher
KNKaryn L. Newman
Karyn L. Newman
JKJay D. Keasling
Jay D. Keasling

10 April 2013 in Nature
Verified
Journal Article
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CPC. J. Paddon
C. J. Paddon
PWP. J. Westfall
P. J. Westfall
DPD. J. Pitera
D. J. Pitera
KBK. Benjamin
K. Benjamin
KFK. Fisher
K. Fisher
JNJ. D. Newman
J. D. Newman
Saccharomyces cerevisiae is engineered to produce high concentrations of artemisinic acid, a precursor of the artemisinin used in combination therapies for malaria treatment; an efficient and practical chemical process to convert artemisinic acid to artemisinin is also developed. Artemisinin-based combination therapies are the treatment of choice for uncomplicated Plasmodium falciparum malaria, but the supply of plant-derived artemisinin can sometimes be unreliable, causing shortages and high prices. This manuscript describes a viable industrial process for the production of semisynthetic artemisinin, with the potential to help stabilize artemisinin supply. The process uses Saccharomyces cerevisiae yeast engineered to produce high yields of artemisinic acid, a precursor of artemisinin. The authors have also developed an efficient and scalable chemical process to convert artemisinic acid to artemisinin. In 2010 there were more than 200 million cases of malaria, and at least 655,000 deaths1. The World Health Organization has recommended artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by the parasite Plasmodium falciparum. Artemisinin is a sesquiterpene endoperoxide with potent antimalarial properties, produced by the plant Artemisia annua. However, the supply of plant-derived artemisinin is unstable, resulting in shortages and price fluctuations, complicating production planning by ACT manufacturers2. A stable source of affordable artemisinin is required. Here we use synthetic biology to develop strains of Saccharomyces cerevisiae (baker’s yeast) for high-yielding biological production of artemisinic acid, a precursor of artemisinin. Previous attempts to produce commercially relevant concentrations of artemisinic acid were unsuccessful, allowing production of only 1.6 grams per litre of artemisinic acid3. Here we demonstrate the complete biosynthetic pathway, including the discovery of a plant dehydrogenase and a second cytochrome that provide an efficient biosynthetic route to artemisinic acid, with fermentation titres of 25 grams per litre of artemisinic acid. Furthermore, we have developed a practical, efficient and scalable chemical process for the conversion of artemisinic acid to artemisinin using a chemical source of singlet oxygen, thus avoiding the need for specialized photochemical equipment. The strains and processes described here form the basis of a viable industrial process for the production of semi-synthetic artemisinin to stabilize the supply of artemisinin for derivatization into active pharmaceutical ingredients (for example, artesunate) for incorporation into ACTs. Because all intellectual property rights have been provided free of charge, this technology has the potential to increase provision of first-line antimalarial treatments to the developing world at a reduced average annual price.

1 June 2003 in Nature Biotechnology
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VMVincent J J Martin
Vincent J J Martin
DPDouglas J Pitera
Douglas J Pitera
SWSydnor T Withers
Sydnor T Withers
JNJack D Newman
Jack D Newman
JKJay D. Keasling
Jay D. Keasling

1 March 2016 in Cell
Verified
Journal Article
Closed access
JNJens Nielsen
Jens Nielsen
JKJay D. Keasling
Jay D. Keasling

27 January 2010 in Nature
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Journal Article
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ESEric J. Steen
Eric J. Steen
YKYisheng Kang
Yisheng Kang
GBGregory Bokinsky
Gregory Bokinsky
ZHZhihao Hu
Zhihao Hu
ASAndreas Schirmer
Andreas Schirmer
JKJay D. Keasling
Jay D. Keasling

2 August 2009 in Nature Biotechnology
Verified
Journal Article
Closed access
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JDJohn E Dueber
John E Dueber
GWGabriel C Wu
Gabriel C Wu
GMG Reza Malmirchegini
G Reza Malmirchegini
TMTae Seok Moon
Tae Seok Moon
CPChristopher J Petzold
Christopher J Petzold
JKJay D. Keasling
Jay D. Keasling