s******9
发帖数: 283 | 1 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. | y****d
发帖数: 46 | 2 我觉得主要就是靠提高了产量。他们的发酵产量已经达到25g/L和很多非常便宜的
抗生素都高了，而且也基本解决了后续的化学催化问题，路径简单、产率较高、操作简
便，可以说清除了大规模商业化生产的大部分障碍。
青蒿素的故事讲了这么多年，到这里可以基本划一个句号了。能发natuer我觉得主
要是因为这个是Synthetic biology第一个真正应用的例子，未来几十年人们提到合成
生物学，这篇文章肯定是有一席之地的，从这个历史的角度讲，发表在natuer上面名至
实归。 | s******9
发帖数: 283 | 3 这篇文章在方法学上有什么新的贡献？比如有一定普适性的方法可以帮助其他天然产物
的合成？就怕是一般的工艺优化，而且只能用于artemisinin。毕竟，没有几个组有
Keasling这样的资源（当然还有时间）。
【在 y****d 的大作中提到】
: 我觉得主要就是靠提高了产量。他们的发酵产量已经达到25g/L和很多非常便宜的
: 抗生素都高了，而且也基本解决了后续的化学催化问题，路径简单、产率较高、操作简
: 便，可以说清除了大规模商业化生产的大部分障碍。
: 青蒿素的故事讲了这么多年，到这里可以基本划一个句号了。能发natuer我觉得主
: 要是因为这个是Synthetic biology第一个真正应用的例子，未来几十年人们提到合成
: 生物学，这篇文章肯定是有一席之地的，从这个历史的角度讲，发表在natuer上面名至
: 实归。
| s********n
发帖数: 2939 | 4 这个主要是Amyris的工作，虽然Newman曾经是Keasling的postdoc。
就像ls所说，这个应用还是很有里程碑意义的。
【在 s******9 的大作中提到】
: 这篇文章在方法学上有什么新的贡献？比如有一定普适性的方法可以帮助其他天然产物
: 的合成？就怕是一般的工艺优化，而且只能用于artemisinin。毕竟，没有几个组有
: Keasling这样的资源（当然还有时间）。
| o*******a
发帖数: 242 | 5 抗青蒿素的虫子出现了。
--------------------
Nat Genet. 2013 Apr 28. doi: 10.1038/ng.2624. [Epub ahead of print]
Multiple populations of artemisinin-resistant Plasmodium falciparum in
Cambodia.
Miotto O, Almagro-Garcia J, Manske M, Macinnis B, Campino S, Rockett KA,
Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Duong S, Nguon C, Chuor
CM, Saunders D, Se Y, Lon C, Fukuda MM, Amenga-Etego L, Hodgson AV, Asoala V
, Imwong M, Takala-Harrison S, Nosten F, Su XZ, Ringwald P, Ariey F, Dolecek
C, Hien TT, Boni MF, Thai CQ, Amambua-Ngwa A, Conway DJ, Djimdé AA, Doumbo
OK, Zongo I, Ouedraogo JB, Alcock D, Drury E, Auburn S, Koch O, Sanders M,
Hubbart C, Maslen G, Ruano-Rubio V, Jyothi D, Miles A, O'Brien J, Gamble C,
Oyola SO, Rayner JC, Newbold CI, Berriman M, Spencer CC, McVean G, Day NP,
White NJ, Bethell D, Dondorp AM, Plowe CV, Fairhurst RM, Kwiatkowski DP.
Source
1] Medical Research Council (MRC) Centre for Genomics and Global Health,
University of Oxford, Oxford, UK. [2] Mahidol-Oxford Tropical Medicine
Research Unit, Mahidol University, Bangkok, Thailand. [3] Wellcome Trust
Sanger Institute, Hinxton, Cambridge, UK.
Abstract
We describe an analysis of genome variation in 825 P. falciparum samples
from Asia and Africa that identifies an unusual pattern of parasite
population structure at the epicenter of artemisinin resistance in western
Cambodia. Within this relatively small geographic area, we have discovered
several distinct but apparently sympatric parasite subpopulations with
extremely high levels of genetic differentiation. Of particular interest are
three subpopulations, all associated with clinical resistance to
artemisinin, which have skewed allele frequency spectra and high levels of
haplotype homozygosity, indicative of founder effects and recent population
expansion. We provide a catalog of SNPs that show high levels of
differentiation in the artemisinin-resistant subpopulations, including codon
variants in transporter proteins and DNA mismatch repair proteins. These
data provide a population-level genetic framework for investigating the
biological origins of artemisinin resistance and for defining molecular
markers to assist in its elimination. | s******s
发帖数: 13035 | 6 是比尔盖子资助的那个么？前几年天朱棣文说过，好像人家给资助的最终目标
是一毛钱一针，做出来就采购一大批去非洲。不过听说，非洲那边有的国家打针
不按要求打联针，整出来很多抗性bug
artemisinin.
【在 s******9 的大作中提到】
: 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
|
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