Bioengineers Use Yeast to Manufacture Drugs

The yeast’s output of noscapine, a cough suppressant naturally made by poppies, is

18,000-fold higher than previous attempts.

Apr 3, 2018
JIM DALEY

KARL GRUBER, WIKIMEDIA

In a study published yesterday (April 2) in PNAS, researchers describe how they

genetically engineered a strain of brewer’s yeast, Saccharomyces cerevisiae, to produce
noscapine, a nonnarcotic cough suppressant produced naturally by opium poppies. The
scientists included an array of genes from various organisms to build the biosynthetic
pathway in the yeast.

“This is a technology that’s going to change the way we manufacture essential

medicines,” says coauthor Christina Smolke, a synthetic biologist at Stanford University, in a
statement “Traditionally, we’ve gotten our medicines from the natural world, mainly from
plants. But the plants’ molecular assembly lines have evolved to optimize the plants’
survival, not to churn out buckets of one substance we humans want to get our hands on.”

Smolke and her colleagues inserted 25 plant, bacteria, and mammalian genes into
the yeast, as well as six yeast genes, to create the noscapine-producing pathway. They
used CRISPR to edit genes so that the enzymes they coded for would work effectively in the
exotic, acidic environment of yeast cells.

The new configuration improved the yeast’s output of the drug by a factor of 18,000
over previous attempts that used different gene combinations. As a result, the scientists can
produce substantial amounts of noscapine in just a few days. This improvement in output
means that the technique could eventually be optimized for commercial manufacturing,
although that requires an additional 100-fold increase in production. Smolke says much of
this can be achieved by simply scaling up laboratory hardware.

Noscapine has traditionally been widely used as a cough suppressant, but in 1998
researchers at Emory University discovered its potential as an anticancer drug. Since then, it
has been shown to reduce and possibly prevent metastasis of breast and prostate tumors in
mice, but the process of harvesting the drug from opium poppies is laborious (via TIME).

“We’re no longer limited to what nature can make,” Smolke says in the statement.
“We’re moving to an age where we can borrow nature’s medicine-manufacturing processes
and, using genetic engineering, build miniature living factories that make what we want.”
 Ancient Protein Helps E. coli Thwart Viral Attack

When engineered to use a four-billion-year-old version of the protein thioredoxin, the

bacteria can stall bacteriophage replication, a new study shows.

May 9, 2017
ASHLEY YEAGER

CDCResurrecting ancient proteins in modern E. coli can protect the bacterium from
viral infection, scientists reported today (May 9) in Cell Reports. Researchers from Spain
engineered the genetic sequences that code for ancestral forms of the protein thioredoxin—
including one that would have existed about 4 billion years ago—and found that not only did
the old protein function in the cells, but when these bacteria were exposed to the
bacteriophage T7, they fended off viral infection.

“This is an interesting strategy that impedes the propagation of the virus,”

biochemist Reinhard Sternerof the University of Regensburg in Germany told The Scientist.
“It could be a new mode of viral resistance, which is pretty cool.”

The project got its start from an interest in plants. Specifically, Asunción Delgado and
colleagues at the University of Granada knew that proteins in plants that aid viral replication
haven’t evolved so much so that they can avoid being hijacked by viruses. So, the team
wondered whether a different version of a protein, possibly an ancestral form, could keep an
organism alive but prevent viral replication.

Thioredoxin was a good test subject: it is found in all modern organisms and is
essential for both hosts and invading viruses. In the new study, Delgago and colleagues
studied the genetic sequences of a range of microbial organisms, traced their ancestry, and
identified the sequences for ancient thioredoxins, dating from 1.5 billion to 4 billion years
ago.

Ancient versions of the thioredoxin protein (green circles) don’t allow viral DNA to
replicate, but the more modern versions (red circles) do.DELGADO ET AL.In E. coli,
thioredoxin circulates electrons to keep vital chemical reactions going. When the team
replaced the modern thioredoxin gene in E. coli with ancient sequences, the resulting
proteins too moved electrons around, with varying degrees of success. The oldest version
didn’t work as well as the more recent ones; but the fact that it dated back to the origin of life
itself and still kept the E. coli alive was surprising, said chemist Jose Sanchez-Ruiz, the
paper’s senior author, in an interview.

The team then mixed the altered E. coli with bacteriophage T7, which normally
recruits thioredoxin in bacteria for help in DNA replication. “The virus inserted its DNA into
the bacterium without any trouble. But, when the virus went to recruit thioredoxin for its own
purposes, that was a problem,” Sanchez-Ruiz said. Thioredoxins that were roughly 2.5
billion years and older couldn’t be used by the virus for DNA replication. The team also tried
the experiment with the human form of thioredoxin, which prevented the virus from
replicating, too.

Swapping a protein essential to both the host organism and the virus infecting that
organism could confer viral resistance. The strategy could be applied to boosting plants’
resistance to viruses, Sanchez-Ruiz said.

“A big hurdle [to deploying ancient proteins in crops] that must be overcome is that
the parts of the protein that do not interact with the pathogen do evolve, albeit more slowly
than the pathogen-associated parts,” wrote Michael Harms, an evolutionary biophysicist at
the University of Oregon, in an email to The Scientist. “As a result, ancestral proteins do not
necessarily directly replace their modern counter parts.”

Harms explained that in commercial plants, growth rate, taste, color, and a number of
other traits are important. An ancestral gene might compromise one of the many desired
traits, even though it might protect against infection. “Because of this, I suspect that
ancestral proteins may be a starting point for engineering more resistant plants rather than a
standalone, turn-key solution.”

A. Delgado et al., “Using resurrected ancestral proviral proteins to engineer virus

resistance.”Cell Reports, doi:10.1016/j.celrep.2017.04.037, 2017
 OPINION

Published October 19

Sketchy Genetic Engineering Practices Could Spell The End of The World As We Know It

By Michael Guillen, Ph.D. | Fox News

Last century, the world was upended when science breached the inner sanctum of
atoms and created the A-bomb. Today we are hacking into the inner sanctum of living cells
and the consequences, for better and worse, spell the end of life as we know it.

Today’s drama began several years ago, when genetic engineers from Harvard, MIT,
and U.C. Berkeley co-developed powerful gene-editing tools that now make it possible for us
to directly monkey with DNA at will. The tools go by the name CRISPR, which stands for –
Clustered Regularly Interspaced Short Palindromic Repeats.

In plain English, CRISPR is making possible scenarios once considered science

fiction. They are unprecedented developments ranging from utopian to dystopian.

First, the good: using CRISPR and other tools to treat genetic diseases, of which
there are thousands – everything from cystic fibrosis, hemophilia, and breast cancer to
diabetes, autism, and even obesity.
 Patients with Duchenne Muscular Dystrophy (DMD), for instance, have a defective
gene that fails to produce enough dystrophin, a key muscle protein. Recently, doctors at
Nationwide Children’s Hospital in Columbus, Ohio, injected healthy genes into four DMD
boys and obtained very encouraging results.

Second, the sketchy: using gene-editing tools to mix and match disparate species.
Please note: this is not your grandfather’s selective-breeding practice.

As I write this, renegade genetic engineers in California and Minnesota are creating
pig-human and sheep-human chimeras whose vital organs are human. They are doing it
against the wishes of and without any funding from the National Institutes of Health (NIH).
But they’re reportedly motivated by a noble cause: to create a limitless source of body parts
for patients in need of them.

But what if the human cells in these illicit chimeras proliferate beyond their vital
organs – to their brains, for instance? The resulting creatures, possibly capable of human
thought, could no longer be considered just pigs.

“We are not near the island of Dr. Moreau, but science moves fast,” warns David
Resnik, an ethicist at the NIH. “The specter of an intelligent mouse stuck in a laboratory
somewhere screaming ‘I want to get out’ would be very troubling to people.”

Hiromitsu Nakauchi – a Stanford University biologist who is trying to make human-

sheep chimeras – concedes such a thing could happen. “If the extent of human cells is 0.5
percent, it’s very unlikely to get thinking pigs or standing [two-legged] sheep,” he says. “But if
it’s large, like 40 percent, then we’d have to do something about that.”

Finally, the unnerving: using CRISPR to create novel organisms from scratch. “We
are going from reading our genetic code to the ability to write it,” declares renowned
geneticist Craig Venter. “That gives us the hypothetical ability to do things never
contemplated before.”
To that end, geneticists recently launched Genome Project-Write (GP-Write), a global
initiative that intends to redesign existing genomes and synthesize living organisms sprung
entirely from the human imagination.
I love science and trust in its motivating desire to understand the universe and
improve the human condition.
 But if we’ve learned anything from our hacking the atomic nucleus, it’s this: the
sketchy and unnerving consequences – such as nuclear power plants and H-bombs –
severely overshadow the good ones, such as nuclear medical devices that treat cancers and
routinely save lives. Witness our current nail-biting efforts to keep nukes out of the hands of
North Korea and Iran.

Although I foresee a great deal of good coming from genetic engineering, I’m inclined
to commiserate with the late Erwin Chargaff, eminent Columbia University biochemist and
DNA research pioneer. “The nucleus of the atom, the nucleus of the cell,” he wrote in
"Heraclitean Fire: Sketches from a Life Before Nature." “In both instances do I have the
feeling that science has transgressed a barrier that should have remained inviolate.”
 REFLECTION

Genetic engineering is defined as the direct manipulation of an organism’s genes

including heritable and nonheritable recombinant DNA constructs It is now a mature field that
made it possible to study, control and manipulate genes in ways that continue to amaze
even those working in the field. The power of the tools that have become available has
resulted in an explosion of discoveries. The development of a technique for the production of
monoclonal antibodies has been an integral part of this revolution. . It aims to enhance the
characteristics or qualities of an organism so that it may adapt to the continuous change in
the environment as well as to meet the growing needs of humans. The major applications
are for the industrial production of desired peptides or proteins, or to alter the biological
capabilites of the organism. These techniques have been used to develop crops with
agronomically useful changes, such as pest resistance and ripening properties that allow for
shipment. Surprising results have been obtained by silencing genes in experimental
organisms, as well as the production of animal models of human disease by deriving strains
of animals with mutated human genes. Much attention is being given to the production of
products and methods to modify an individual's cells to treat human disease.

The development of genetic engineering has increased notably in the last few years.
Some people support the investment in this field whereas others are against too. People
who are supporting it argue that for instance farmers could have crops more resistant to
insects and diseases, and many genetically modified crops can grow faster. These
advantages can be extremely positive for food production in developing nations where
people starve. Fasters growing cereals, fruits and vegetables would mean more profit.
Moreover, some medicines and vaccines are obtained throw genetic engineering process.
An important breakthrough that genetic engineering can help society to fight with inherited
diseases thus, prolong one’s life. Some genes can be modified before a baby is born
improving its life. Genetic engineering has also found its way to the medical field which is a
huge help in curing some diseases and in the process of developing vaccines for some
known incurable diseases such as cancer. However, there are ethical concerns about its
use. Some ecologists warn about the disaster consequences to the Earth. They say that
genetically modified crops can affect seriously whole ecosystems as it disrupts the food
chain if crops are more resistant to predators. Furthermore, there are certain issues that
made genetic engineering a negative process. Human genetic engineering arises many
arguments as it is considered unethical and therefore violates human rights. It is somehow
unacceptable to manipulate human characteristics as it is unnatural and against to religious
beliefs. Society and human evolution would completely change. It is feared that our genetic
ambitions would outpace our safeguards. These new techniques can leverage "selfish"
genes that force organisms to pass modifications to offspring. Put simply, we can now wipe
out entire species with a single mistake. Aside from this, a wrong move in genetic
manipulation can cause pandemic destructions. Although genetic engineering is used to
cure or eliminate diseases, on the other hand, it can also be the source of a new developing
diseases which can be more complex than the existing ones and can therefore wipe
mankind.

Genetic engineering has its pros and cons. Although its main goal is for
development, it is inevitable for such complicated field to arise without negative effects.
Nothing can be made perfect, there is always a slight flaw in every scientific discoveries. For
such advance tool like genetic engineering, it comes with great responsibility. We must know
our limitations because if we exceed to our limits, we may also be the one to cause harm to
ourselves and to the society we are involved in. We should bear in mind that not everything
can go our way thus, we must accept things the way they are and be contented of what was
given to us by the Creator.