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Para ilmuwan menghasilkan obat kanker dari tanaman langka di laboratorium

Date:

September 10, 2015

Source:

Stanford University

Summary:

Ilmuwan Stanford menghasilkan obat kanker umum - sebelumnya hanya tersedia dari tanaman yang terancam punah - di sebuah  laboratorium tanaman umum . Karya ini dapat menyebabkan pasokan lebih stabil dari obat dan memungkinkan para ilmuwan untuk memanipulasi obat yang membuatnya lebih aman dan lebih efektif .

............ Sekarang Elizabeth Sattely , asisten profesor teknik kimia di Stanford , dan mahasiswa pascasarjana  Warren Lau telah mengisolasi mesin untuk membuat obat melawan kanker yang banyak digunakan dari tanaman yang terancam punah . Mereka kemudian menempatkan mesin yang menjadi umum , tanaman laboratorium yang mudah tumbuh , yang mampu menghasilkan bahan kimia ......more

Scientists produce cancer drug
from rare plant in lab

Date:

September
10, 2015

Source:

Stanford
University

Summary:

Stanford scientists produced a common
cancer drug -- previously only available from an endangered plant -- in a
common laboratory plant. This work could lead to a more stable supply of the
drug and allow scientists to manipulate that drug to make it even safer and
more effective.

.................

Many of the drugs we take today to treat
pain, fight cancer or thwart disease were originally identified in plants, some
of which are endangered or hard to grow. In many cases, those plants are still
the primary source of the drug.

Now Elizabeth Sattely, an assistant
professor of chemical engineering at Stanford, and her graduate student Warren
Lau have isolated the machinery for making a widely used cancer-fighting drug
from an endangered plant. They then put that machinery into a common, easily
grown laboratory plant, which was able to produce the chemical. The technique
could potentially be applied to other plants and drugs, creating a less
expensive and more stable source for those drugs.

"People have been grinding up
plants to find new chemicals and testing their activity for a really long
time," Sattely said. "What was striking to us is that with a lot of
the plant natural products currently used as drugs, we have to grow the plant,
then isolate the compound, and that's what goes into humans."

In her work, published Sept. 10 in the
journal Science, Sattely and her team used a novel technique to identify
proteins that work together in a molecular assembly line to produce the cancer
drug. Her group then showed that the proteins could produce the compound
outside the plant -- in this case, they had put the machinery in a different
plant, but they hope to eventually produce the drug in yeast. Either the plant
or yeast would provide a controlled laboratory environment for producing the
drug.

This work could lead to new ways of
modifying the natural pathways to produce derivative drugs that are safer or
more effective than the natural source.

"A big promise of synthetic biology
is to be able to engineer pathways that occur in nature, but if we don't know
what the proteins are, then we can't even start on that endeavor," said
Sattely, who is also a member of the interdisciplinary institutes Stanford
Bio-X and Stanford ChEM-H.

Finding the machinery

The drug Sattely chose to focus on is
produced by a leafy Himalayan plant called the mayapple. Within the plant, a
series of proteins work in a step-by-step fashion to churn out a chemical
defense against predators. That chemical defense, after a few modifications in
the lab, becomes a widely used cancer drug called etoposide.

The starting material for this chemical
defense is a harmless molecule commonly present in the leaf. When the plant
senses an attack, it begins producing proteins that make up the assembly line.
One by one, those proteins add a little chemical something here, subtract
something there, and after a final molecular nip and tuck, the harmless starting
material is transformed into a chemical defense.

The challenge was figuring out which of
the many proteins found in the mayapple leaf were the ones involved in this
pathway. Sattely started with the realization that the proteins she needed to
find weren't always present in the leaf. "It's only when the leaf is
wounded that the molecule is made," she said.

And if the molecule is only made after
wounding, the proteins that make that molecule are probably also only around
after a wound as well.

The question then became, "What are
all the molecules that are there after wounding?" Sattely said.

It turns out that after damaging the
plant leaf, 31 new proteins appeared. Sattely and her team put various
combinations of those proteins together until they eventually found 10 that
made up the full assembly line. They put genes that make those 10 proteins into
a common laboratory plant, and that plant began producing the chemical they
were seeking.

Drugs from yeast

The eventual goal is not simply moving
molecular machinery from plant to plant. Now that she's proven the molecular
machinery works outside the plant, Sattely wants to put the proteins in yeast,
which can be grown in large vats in the lab to better provide a stable source
of drugs.

Producing a drug in yeast also provides
some flexibility that isn't present when isolating a drug from plants.

"We can only use what the plant
gives us," Sattely said.

In yeast, scientists can modify the
genes to produce proteins with slightly different functions. For example, they
could nip a little more off the chemical or add a slightly bigger side chain,
or subtly alter the function of the eventual drug.

It may also be possible to feed the
yeast a slightly different starting product, thereby changing the chemical that
the molecular assembly line churns out. These approaches would provide a way of
tweaking existing drugs in an effort to improve them.

Sattely said the work is a good example
of how chemistry can be applied to problems of human health, which is the goal
of Stanford ChEM-H. She thinks the technique she developed to find the pathway
in mayapple could be applied to a wide range of other plants and drugs.

"My interests are really
identifying new molecules and pathways from plants that are important for human
health," she said.







Story Source:

The above post is reprinted from materials provided byStanford University. The original item was written by Amy Adams. Note:
Materials may be edited for content and length.







Journal Reference:

1.   
Warren Lau and Elizabeth S.
Sattely. Six enzymes from mayapple that complete the biosynthetic
pathway to the etoposide aglycone. Science, September 2015 DOI:10.1126/science.aac7202

http://www.sciencedaily.com/releases/2015/09/150910144044.htm

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