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Searching Genomes for New Chemotherapies

Searching Genomes for New Chemotherapies

A new hunting ground for medically important compounds may be the genome of a stressed-out, poisonous evergreen shrub. Rhazya stricta is a relative of a plant currently mined for chemotherapies and holds promise for future cancer therapies, according to scientists at The University of Texas at Austin, King Abdulaziz University (KAU) in Saudi Arabia and two institutions in Canada, University of Ottawa and Université de Montréal.

Evergreen Rhazya stricta flowers. Image courtesy of Tracey Ruhlman

New research on the nuclear genome sequence of R. stricta was published in the current edition of Nature Scientific Reports.

Chemicals created by plants are an important source of material for the vast majority of the medicines we use today. Plants produce these chemicals, or secondary compounds, by complex pathways in response to the stress of changing environmental conditions. Plants that share an evolutionary history also share related collections of these compounds.

"Plants are subject to environmental stressors, and they respond to stress by producing secondary compounds," says Tracey Ruhlman, a Research Scientist in the Department of Integrative Biology at UT Austin and corresponding author on the paper. "For example, some of the alkaloids found in Rhazya likely evolved to protect it from the hot, dry conditions in Western Asia where it flourishes."

Rhazya stricta is one of 4,500 species of plants in the milkweed, or Apocynaceae, family. This family shares pathways that have yielded thousands of alkaloid compounds including those from Catharanthus roseus (periwinkle), alkaloids that are currently used in chemotherapy protocols for leukemia and Hodgkin's lymphoma. While these treatments are effective, it is extremely difficult to replicate the complicated pathway that produces the alkaloid compounds in a laboratory; currently these compounds are extracted from plants. Different but related species—like R. stricta—might provide alternative pathways to medically useful compounds.

"There is a dearth of genomic information about plants that make these kinds of alkaloids," Ruhlman says.

"There is a lot of interest in doing genetic engineering to modify plants so they can produce more compounds that we need," says Robert Jansen, the Sidney F. and Doris Blake Centennial Professor in Systematic Botany and the Blake Collection at UT Austin, noting also that this will require a thorough understanding of the naturally occurring compounds that various plants produce in response to their environment.

Ruhlman's team collected the seeds from R. stricta in Makkah Province, Saudi Arabia and germinated the seeds in the greenhouses at UT Austin. The nuclear genome of R. stricta is deposited in GenBank, and a database highlighting the genes behind potentially important pathways is available online. The team plans on developing the genomic resources for 29 other species of plants from Saudi Arabia.

"The collaboration between UT-Austin and KAU began in 2011, and we plan to explore additional plants in other plant families that produce compounds of potential pharmaceutical value," says Jamal Sabir, Director of the Biotechnology Research Group and Professor of Biological Sciences at KAU."Prospecting the genomes of plants for chemical compounds will be an important part of the development of new medicines in the future."

Financial assistance for this research came from KAU's Vice President for Educational Affairs Prof. Dr. Abdulrahman O. Alyoubi and the Deanship of Scientific Research (Unit of Strategic Technologies Research Number 431/008-D). Additional assistance came from UT Austin: Texas Advanced Computing Center, the Plant Resources Center and Scott Hunicke-Smith at the Genome Sequence and Analysis Facility.

Rhayza stricta in the field. Image courtesy of Tracey Ruhlman
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Saturday, 04 February 2023

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