Microbial synthesis of therapeutic bile acids for alzheimer's disease
Active Project Grant Awarded Last action
- Award ID
- R42AG083665
- Recipient
-
Metselex Inc. UEI JTLUDAMC9CK1
- Awarding agency
-
National Institute on Aging
National Institutes of Health, Department of Health and Human Services
- Obligated
- $4,251,819
Award facts
- Assistance listing
- 93.866 Aging Research
- Completion date 89% complete
- Originally
- Place of performance
- Minnesota, USA
Award details come from USAspending.gov.
Description
- Abstract
- This phase sttr phase II proposal aims to engineer and scale-up a synthetic metabolic pathway in a microbial host to produce udca and related compounds. Additionally, the udca produced from the engineered synthetic metabolic pathway will be used to synthesize derivatives for testing in our alzheimer's disease cell and animal models. The proposed work has high intellectual merit for the following reasons: (i) udca biosynthesis does not occur in any organism whose cultivation can be scaled to meet global demand, (II) udca requires a multi- organism biosynthetic pathway (animal cholic acids converted to udca by the GUT microbiome) that will have to be reconstituted in a single cell, and (III) the anticipated scale and complexity of this engineering effort (combining more than a dozen genes from four organisms) are on the edge of what is feasible. Technical hurdles involve the discovery of new enzymes that convert ergosterol to cholesterol (a process known to exist in brine shrimp), achieving proper localization and enzymatic activity for fifteen recombinant gene products in yeast, and balancing the expression levels of each gene to support high-titer production of udca in yeast. The combined metselex/university of minnesota team will overcome these hurdles using their platform for multi-gene pathway refactoring and high-throughput DNA assembly and analytical methods. Experience with these tools/approaches and success in engineering similar synthetic metabolic pathways qualifies this team conduct these studies and will enable them to accomplish their phase II goals.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $283,246 | |
| Amendment | $1,280,101 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $1,344,236 | |
| Original award | $1,344,236 |
Quick answers
Who received award R42AG083665?
R42AG083665 was awarded to Metselex Inc. by National Institute on Aging (National Institutes of Health) on June 1, 2020.
How much is award R42AG083665 worth?
$4,251,819 has been obligated on R42AG083665.
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