# Microbial Synthesis of Therapeutic Bile Acids

> **NIH NIH R41** · METSELEX, INC. · 2020 · $450,234

## Abstract

ABSTRACT
This Phase STTR Phase I proposal aims to engineer a synthetic metabolic pathway in a microbial host to produce
UDCA and related compounds. 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 I goals.

## Key facts

- **NIH application ID:** 10010076
- **Project number:** 1R41NS113732-01A1
- **Recipient organization:** METSELEX, INC.
- **Principal Investigator:** DEZHI LIAO
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,234
- **Award type:** 1
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10010076

## Citation

> US National Institutes of Health, RePORTER application 10010076, Microbial Synthesis of Therapeutic Bile Acids (1R41NS113732-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10010076. Licensed CC0.

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