Page 20 - Abacoa Community News - February '24

Page 20, Abacoa
scieNce oN tHe cuttiNg edge

bonds and replace them with more reactive carbon-oxygen where it would be open to science. His team is now
bonds. For a long time, the scientists couldn’t understand developing ways to study the strains, read their genomes and
Scientists Discover Key To how the bacteria managed that feat. deposit the information into a searchable database for the
scientific community to access. Modern genome sequencing
Cracking the mystery involved finding other tiancimycin

A Potential Natural Cancer A-like natural product-producing bacteria among the and bioinformatics techniques are proving that there may
institute’s Natural Products Discovery Center collection of
be as many as 30 interesting gene clusters in each strain
Treatment’s Potency 125,000 bacterial strains, and analyzing their genomes to of bacteria they study, and many of them code for natural
search for the evolutionary hints. products never before documented by scientists, said Shen,
Slumbering among thousands of bacterial strains in a The historic collection had long been housed in a who is a member of the UF Health Cancer Center.
collection of natural specimens at The Herbert Wertheim UF pharmaceutical company’s basement, collected over The discovery of the new cofactorless oxygenases is
Scripps Institute for Biomedical Innovation & Technology, decades following the discovery of penicillin in the scientific but the latest example of the chemical riches that lie within
several fragile vials held something unexpected, and possibly community’s hopeful rush to find the next great antibiotic. The Wertheim UF Scripps Institute’s collection, Shen said.
very useful. The collection did generate several historically important Their discovery has sparked new excitement about further
Writing in the journal Nature drugs through the years, including the tuberculosis antibiotic investigating the reasons the unique chemistry evolved, and
Chemical Biology, a team led streptomycin and the organ transplant drug sirolimus. But the ways it may prove useful.
by chemist Ben Shen, Ph.D., the majority of the collection’s freeze-dried bacterial strains “This publication underscores how many surprises
described discovery of two new had rested in their glass vials, unexplored. nature still has for us,” Shen said, “It can teach us much
enzymes, ones with uniquely In 2018, Shen won a competition for the collection, so
useful properties that could that it could be fully investigated in an academic setting, Scientists Discover Key on page 21
help in the fight against human
diseases including cancer. The
discovery, published last week,
offers potentially easier ways to Chemistry professor Ben
study and manufacture complex Shen, Ph.D., directs the
natural chemicals, including Natural Products Discovery
those that could become Center at The Herbert
medicines. Wertheim UF Scripps
The contribution of Institute for Biomedical
bacterial chemicals to the Innovation & Technology.
history of drug discovery is The center holds one of the
remarkable, said Shen, who world’s largest collections of
directs the Natural Products microbial natural chemicals.
Discovery Center at the Photo by Scott Wiseman
institute, one of the world’s
largest microbial natural product collections.
“Few people realize that nearly half of the FDA-approved
antibiotics and anticancer drugs on the market are natural
products or are inspired by them,” Shen said. “Nature is the
best chemist to make these complex natural products. We are
applying modern genomic technologies and computational tools
to understand their fascinating chemistry and enzymology, and
this is leading to progress at unprecedented speed. These enzymes
are the latest exciting example.”
The enzymes the team discovered have a descriptive, if
unwieldy, name. They are called “cofactorless oxygenases.”
This means the bacterial enzymes pull oxygen from the air
and incorporate it into new compounds, without requiring
the typical metals or other cofactors to initiate the necessary
chemical reaction.
This new way of synthesizing defensive substances
would confer a survival advantage, enabling the organism
to fend off infections or invaders. And because enzymes are
to chemists what drill bits or saw blades are to a carpenter,
they offer scientists new ways to create useful things, said
the paper’s first authors, postdoctoral researchers Chun Gui,
Ph.D., and Edward Kalkreuter, Ph.D.
Most immediately, the discovery of the enzymes, TnmJ
and TnmK2, solves a lingering mystery of how a potential
antibiotic and anticancer compound the Shen lab had first
discovered in 2016, tiancimycin A, achieved such potency,
Gui and Kalkreuter said.
The enzymes enable the bacteria to produce compounds
for targeting and breaking up DNA, Gui said. This would be
immensely useful in fighting off a virus or other germ — or
killing cancer.
Tiancimycin A
is being developed
as part of a cancer-
targeting antibody
therapy. These
types of combined
antibody-drug
therapeutics Within the glass vials of the Natural
represent a rapidly Products Discovery Center at The
grow ing new Herbert Wertheim UF Scripps
approach to fighting Institute for Biomedical Innovation &
cancer . But a Technology, scientists have discovered
critical step to using two useful new enzymes which may
tiancimycin A as an help them create medicines for cancer
antibody’s payload and other conditions.
is making enough to
study it at a larger scale. That proved challenging.
“Even after we identified genes responsible for
encoding tiancimycin A, several of the steps required
to synthesize it could not be predicted,” Gui said. “The
two enzymes described in the current study are highly
unusual.”
Tiancimycin A was first found in a soil-dwelling bacteria,
a type of streptomyces from the strain collection at the
Natural Products Discovery Center. To make its powerful
chemical weapon, the organism had to solve a problem. It
somehow had to break three highly stable carbon-carbon