Synthetic biology to discover kratom natural product biosynthetic pathways for biased analgesic development
Active Project Grant Awarded Last action
- Award ID
- R01AT012633
- Recipient
-
Cornell University UEI G56PUALJ3KT5
- Awarding agency
-
National Center for Complementary and Integrative Health
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,739,147
Award facts
- Assistance listing
- 93.213 Research and Training in Complementary and Integrative Health
- Completion date 50% complete
- Place of performance
- Ithaca, NY 14853, USA
Award details come from USAspending.gov.
Description
- Abstract
- Opioid alternative analgesics that would kill pain potently without the respiratory side effect will be of specific importance in addressing the opioid crisis. The medicinal herb kratom (mitragyna speciosa) produces natural products (mitragynine and 7-hydroxymitragynine) that selectively activate analgesia only, which are promising "biased" opioid alternatives. Elucidating the kratom biosynthetic pathway composed of enzymes catalyzing sequential reactions toward the syntheses of mitragynine, 7-hydroxymitragynine, or other kratom products is important to the development of "biased" non-opioid analgesics. We propose to identify and reconstruct both the kratom biosynthetic pathways and the plant enzyme complexes organizing plant biosynthesis in yeast by integrating plant functional genomics analysis and synthetic biology. The research will provide new chemical and plant biology knowledge to a broader community, develop a post-translational level understanding of plant pathway regulation in yeast, and highlight the possibility of using synthetic biology to understand how nature achieves complicated natural product biosynthesis. This proposal will develop the conceptual framework to understand how nature organizes the specialized metabolism in plant toward high efficiency and complexity. The development of high-throughput protein-protein interaction method in yeast for plant complex identification will provide new methods and knowledge for plant pathway discovery and reconstruction. The methods and knowledge we develop toward these goals will also enable the structural elucidation, biological activity evaluation, and microbial production of biased opioid alternatives, leading to the development of next-generation painkillers to address the opioid crisis.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $463,781 | |
| Amendment | $420,542 | |
| Amendment | $427,412 | |
| Original award | $427,412 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Boyce Thompson Institute For Plant Research Inc. | $94,527 | |
| Boyce Thompson Institute For Plant Research Inc. | $94,527 | |
| Boyce Thompson Institute For Plant Research Inc. | $94,527 |
Quick answers
Who received award R01AT012633?
R01AT012633 was awarded to Cornell University by National Center for Complementary and Integrative Health (National Institutes of Health) on June 6, 2024.
How much is award R01AT012633 worth?
$1,739,147 has been obligated on R01AT012633.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award