Within an Antarctic sea squirt, scientists discover a bacterial species
with promising anti-melanoma properties
New study brings important advances for Antarctic science and natural
products chemistry

Date:
December 1, 2021
Source:
Desert Research Institute
Summary:
Biologists have successfully traced a naturally-produced melanoma-
fighting compound called 'palmerolide A' to its source: a microbe
that resides within Synoicum adareanum, a species of ascidian
common to the waters of Antarctica's Anvers Island archipelago.



FULL STORY ========================================================================== There are few places farther from your medicine cabinet than the tissues
of an ascidian, or "sea squirt," on the icy Antarctic sea floor -- but
this is precisely where scientists are looking to find a new treatment
for melanoma, one of the most dangerous types of skin cancer.


==========================================================================
In a new paper that was published today in mSphere, a research team from
DRI, Los Alamos National Laboratory (LANL), and the University of South
Florida (USF) made strides toward their goal, successfully tracing a naturally-produced melanoma-fighting compound called "palmerolide A" to
its source: a microbe that resides within Synoicum adareanum, a species of ascidian common to the waters of Antarctica's Anvers Island archipelago.

"We have long suspected that palmerolide A was produced by one of the
many types of bacteria that live within this ascidian host species,
S. adareanum," explained lead author Alison Murray, Ph.D., research
professor of biology at DRI. "Now, we have actually been able to identify
the specific microbe that produces this compound, which is a huge step
forward toward developing a naturally-derived treatment for melanoma."
The bacterium that the team identified is a member of a new and previously unstudied genus, Candidatus Synoicihabitans palmerolidicus. This advance
in knowledge builds on what Murray and her colleagues have learned across
more than a decade of research on palmerolide A and its association
with the microbiome (collective suite of microbes and their genomes)
of the host ascidian, S. adareanum.

In 2008, Murray worked with Bill Baker, Ph.D., professor of chemistry
at USF and Christian Riesenfeld, Ph.D., postdoctoral researcher at DRI
to publish a study on the microbial diversity of a single S. adareanum organism. In 2020, the team expanded to include additional researchers
from LANL, USF, and the Universite' de Nantes, and published new work identifying the "core microbiome" of S. adareanum -- a common suite of
21 bacterial species that were present across 63 different samples of
S. adareanum collected from around the Anvers Island archipelago.

In the team's latest research, they looked more closely at the core
microbiome members identified in their 2020 paper to determine which
of the 21 types of bacteria were responsible for the production of
palmerolide A. They conducted several rounds of environmental genome sequencing, followed by automated and manual assembly, gene mining,
and phylogenomic analyses, which resulted in the identification of the biosynthetic gene cluster and palmerolide A-producing organism.

"This is the first time that we've matched an Antarctic natural product
to the genetic machinery that is responsible for its biosynthesis,"
Murray said. "As an anti-cancer therapeutic, we can't just go to
Antarctica and harvest these sea squirts en masse, but now that we
understand the underlying genetic machinery, it opens the door for
us to find a biotechnological solution to produce this compound."
"Knowing the producer of palmerolide A enables cultivation, which will
finally provide sufficient quantity of the compound for needed studies
of its pharmacological properties," added Baker.

Many additional questions remain, such as how S. adareanum and its
palmerolide- producing symbiont are distributed across the landscape
in Antarctic Oceans, or what role palmerolide A plays in the ecology of
this species of ascidian.

Likewise, a detailed investigation into how the genes code for the
enzymes that make palmerolide A is the subject of a new report soon to
be published.

To survive in the harsh and unusual environment of the Antarctic sea
floor, ascidians and other invertebrates such as sponges and corals
have developed symbiotic relationships with diverse microbes that play
a role in the production of features such as photoprotective pigments, bioluminescence, and chemical defense agents. The compounds produced
by these microbes may have medicinal and biotechnological applications
useful to humans in science, health and industry. Palmerolide A is one
of many examples yet to be discovered.

"Throughout the course of disentangling the many genomic fragments
of the various species in the microbiome, we discovered that this
novel microbe's genome appears to harbor multiple copies of the genes responsible for palmerolide production," said Patrick Chain, Ph.D.,
senior scientist and Laboratory Fellow with LANL. "However the role
of each copy, and regulation, for example, are unknown. This suggests palmerolide is likely quite important to the bacterium or the host, though
we have yet to understand it's biological or ecological role within this Antarctic setting." "This is a beautiful example of how nature is the
best chemist out there," Murray added. "The fact that microbes can make
these bioactive and sometimes toxic compounds that can help the hosts to facilitate their survival is exemplary of the evolutionary intricacies
found between hosts and their microbial partners and the chemical
handshakes that are going on under our feet on all corners of the planet." ========================================================================== Story Source: Materials provided by Desert_Research_Institute. Original
written by Kelsey Fitzgerald. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Alison E. Murray, Chien-Chi Lo, Hajnalka E. Daligault, Nicole
E. Avalon,
Robert W. Read, Karen W. Davenport, Mary L. Higham, Yuliya Kunde,
Armand E. K. Dichosa, Bill J. Baker, Patrick S. G. Chain. Discovery
of an Antarctic Ascidian-Associated Uncultivated Verrucomicrobia
with Antimelanoma Palmerolide Biosynthetic Potential. mSphere,
2021; DOI: 10.1128/mSphere.00759-21 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211201133645.htm

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