Nature paper on artemisinin semi-synthetic production# Biology - 生物学
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很久以前从yeast转到E.coli合成，现在又是在yeast。有牛人评论一下为什么还能发
Nature？就靠提高了产量和Keasling的名头？这么多年，投入多少钱和人啊。。。
中间体artemisinic acid看起来不很复杂，化学方法真的很难？
High-level semi-synthetic production of the potent antimalarial artemisinin.
http://www.nature.com/nature/journal/v496/n7446/full/nature1205
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.
Nature？就靠提高了产量和Keasling的名头？这么多年，投入多少钱和人啊。。。
中间体artemisinic acid看起来不很复杂，化学方法真的很难？
High-level semi-synthetic production of the potent antimalarial artemisinin.
http://www.nature.com/nature/journal/v496/n7446/full/nature1205
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.
