# Biosensor-driven Platforms for Biosynthesis of Natural Products in Bacteria

> **NIH NIH R35** · UNIVERSITY OF GEORGIA · 2024 · $393,122

## Abstract

Project Summary
As the progress on the development of biosensors, genetic control tools and genetic circuits in the past few years
enabled advanced and sophisticated dynamic control of biosynthesis for optimal production performance in
bacteria, its lack of broad applicability in enhancing natural product biosynthesis is becoming into a major
problem since such dynamic control highly relies on specific biosensors. However, such biosensors are not
always available for most natural products. Within this MIRA research program, the PI aims to bridge these gaps
by developing platforms with broad applicability in improving biosynthesis of a broad spectrum of natural products
including polysaccharides, terpenoids and plant polyketides in bacteria. To reach this goal, the following four
coherent themes will be investigated: 1) engineering and characterizing a series of biosensors for monitoring
and responding to central metabolism in bacteria; 2) developing dynamic control strategies to manage conflict
between growth and production, which can serve as a platform to support efficient biosynthesis of
polysaccharides, human milk oligosaccharides and glycosylated compounds; 3) developing dynamic control
strategies to improve product yield by reducing carbon loss, which can serve as a platform to support high-level
biosynthesis of terpenoids and many other acetyl-CoA derived products; 4) developing dynamic control
strategies to coordinate precursor supplies, which could serve as a platform to support efficient biosynthesis of
plant polyketides. The proposed research program is expected to advance dynamic control of natural product
biosynthesis in bacteria to a whole new level. With these studies, we will greatly enhance the availability of
biosensors targeting central metabolism. We will gain new insights into carbon flux distribution in cellular
metabolism at various conditions through biosensor-aided observation and further understand the interaction of
central metabolism with heterologous biosynthesis during the dynamic processes. Furthermore, the knowledge
gained in this research program will continue to advance the understanding of how to seamlessly implement
artificial logics and functions in native cellular context.

## Key facts

- **NIH application ID:** 10763699
- **Project number:** 2R35GM128620-06
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Yajun Yan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $393,122
- **Award type:** 2
- **Project period:** 2018-09-01 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763699

## Citation

> US National Institutes of Health, RePORTER application 10763699, Biosensor-driven Platforms for Biosynthesis of Natural Products in Bacteria (2R35GM128620-06). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10763699. Licensed CC0.

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