The Pharmacist / Fall-Winter 2023 / Volume 1 / Issue 1

COLLEGE NEWS
Multi-omics Approach Unlocks Discovery
of Natural Products from Bacteria
BY ROB MITCHUM
Many of today’s most useful drugs were originally
discovered in the natural world. After Alexander Fleming
famously discovered penicillin in a moldy petri dish,
scientists probed the microbial world of bacteria and
fungi for new disease-fighting compounds, as well as
products useful in agriculture and industry.
But the laboratory screening process for finding
natural products in bacteria is slow and
struggles to find novel compounds. In a new
paper published by the Proceedings of the
National Academy of Sciences, a team
led by Alessandra Eustaquio of the
UIC College of Pharmacy describes
a powerful new combination of
approaches.
“Traditional pipelines for natural
product discovery tend to rediscover
compounds that we already know,”
said Eustaquio, an associate professor
of pharmaceutical sciences. “My lab is
interested in using genomics to identify and
predict what natural products bacteria should be
able to make and then using genetic methods to try
to obtain the compound.”
Multi-omics is the combination of genomic
data with data on other biological systems,
such as gene transcripts or proteins
present in cells. Eustaquio’s paper
applies a multi-omics approach to a
strain of Burkholderia, a bacterial
genus found in soil. Scientists
at Pfizer—where Eustaquio
previously worked—used
the bacterium to produce
an antitumor agent called
spliceostatin, currently in
preclinical studies. But the
fully sequenced genome of
Burkholderia suggests it has
genes to make as many as
28 additional compounds
with potential human uses,
Eustaquio said.
Her laboratory utilized metabolomic data to
determine which of these products were made in
detectable quantities by Burkholderia. They found
antifungal and anticancer compounds previously
detected in other bacteria and identified a new
product in collaboration with chemist Roger
Linington at Simon Fraser University that they named
selethramide, a peptide that helps the bacteria move.
While preliminary tests showed some antibiotic
activity, the true applications of this new product will
require more investigation.
“One of the pros of finding antibiotics through
traditional screening is that you only find what you’re
interested in,” Eustaquio said. “But you’re always
starting the other way around with genomes, where
it’s more difficult to predict what the activity of that
natural product will be.”
The multi-omics approach also enables Eustaquio’s
group to study how Burkholderia could be used as
a vehicle for synthetic biology and the large-scale
production of natural products.
“My motivation is to understand the bacteria and
develop tools to engineer it,” Eustaquio said. “What
we’re trying to do now is to develop Burkholderia as
a host organism, or what people call a
synthetic biology chassis, where we
can find genes of interest in other
bacteria, transfer those genes
into our host and have it make
products of interest.”
The study involved
graduate students Sylvia
Kunakom and Sean
Romanowski and
postdoc Bruno Paulo
at UIC and postdoc
Sanghoon Lee and
graduate students
Michael Recchia,
Dennis Liu, and
Hannah Cavanagh
at Simon
Fraser.
Alessandra Eustaquio
4 THE PHARMACIST PHARMACY.UIC.EDU