Engineers reprogram yeast cells into microscope drug factory

Since ancient times, in almost all continental cultures, chewing, brewing, or rubbing the leaves of certain plants on various plants can alleviate various diseases, cause hallucinations, and even death at high doses. I have found Today, pharmaceutical companies import these once-unusual plants from specialized farms and extract active chemical compounds to make drugs like scopolamine, atropine, and others that relieve motion sickness and postoperative nausea and are associated with Parkinson’s disease. Place on COVID-19 patients and ventilators that are controlling drooling or maintaining cardiac function during intubation.

Now, Stanford engineers are working on a completely modern way by genetically reprogramming the cell machinery of special yeast strains, effectively converting them into microscope factories that convert sugars and amino acids into these folk medicines. Reproduce these ancient remedies at. Brewery yeasts can naturally convert sugars to alcohol.

“The drug deficiencies seen before and after the COVID-19 crisis find out why there is a need for new and reliable ways to source these plant-based medicines. It could take months or years, and natural disasters and geopolitical issues from some climate-changing countries could disrupt supply.” Nature..

Prashanth Srinivasan, a graduate student in Smolke’s lab and the lead author of this paper, reprogrammed the yeast factory. From an engineer’s point of view, he added each of the yeast organelles or basic metabolic units, Assembly line.. He imagined the nucleus as a factory management center and regulated it in stages Chemical process Necessary for assembling medicines. Energy-generating organelles, mitochondria, demanded special attention. Cells use electrons to hook and unhook molecules on the assembly line, and Srinivasan needed them a lot in order to make the product he wanted, a family of complex chemicals called tropane alkaloids. Humans have been using these compounds for thousands of years, from alleviating toothache and abdominal pain to conducting Religious ceremony And addicted rivals.

Long history of use

The broad medicinal properties of tropane alkaloids are coincidences of coevolution. The two chemicals Plant family— Cocaine, cocaine producers, and nightshades such as Henbein, tobacco, tomato, and pepper have evolved to protect themselves from insects and animals, and happen to be fully integrated into key cellular receptors in the mammalian nervous system. It conforms. These acetylcholine or ACh receptors help convert nerve impulses into action by muscles, glands, and other human tissues. When tropane alkaloids enter the bloodstream, they bind to these ACh receptors, stimulating or inhibiting adjacent muscle, glands, or tissues, resulting in diverse and widespread effects.

Traditional societies did not understand the biochemistry of these compounds, but they realized they had medicinal properties. Native Andeans chewed and brewed tea from coca leaves to reduce hunger, treat gastrointestinal illnesses, and recreation. From Europe to North Africa and West Asia, people favored the tropane alkaloids from the deadly nightshade, or Atropa belladonna, named for its use by women as a pupil dilation cosmetic. Modern ophthalmologists still use it during eye examinations to elicit the same effect. In Southeast Asia, tropane alkaloids from Datura are ingested orally for sinus infections, and people in Aboriginal Australia are based on the hallucinogenic effects of shrub duboisia, the main source of tropane alkaloids for drugs today It is based on the ritual.

Metabolic engineering

Over three years, Smolke and her team made a total of 34 genetic modifications to yeast DNA, controlling each step of the invisible chemical assembly process of tropane alkaloids. Their approach, called metabolic engineering, is a more precise form of biotechnology in which genetic reprogramming uses or modifies naturally occurring cellular processes to produce products that meet human needs. For example, when brewer’s yeast produces alcohol, the cells naturally excrete chemicals that can be collected and drunk. The Stanford team carefully engineered the artificial yeast organelles and membranes to ensure that the complex tropane alkaloid molecule emerged intact from the chemical assembly line and was useful for medicines.

Smolke, who previously bioengineered yeast to produce a different family of plant-based analgesics, received from Stanford to move the amounts of pharmaceuticals produced in these cell factories into full-scale production. We co-founded a biotechnology startup to license the technology, which we expect to take about two years.

“Plants are the best chemists in the world,” Smolke said. “We would like to summarize their unique and useful chemistry in domesticated microorganisms and to build complex molecules inspired by nature, but tailored to meet better. Human needs”