# Harnessing light and model endosymbiosis to produce natural products

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2022 · $295,069

## Abstract

Project Abstract
 A large portion of important drugs and pharmaceutical intermediates either originate from plants or are
synthesized from petrochemical-based products. Several natural products of significantly high value to human
life (e.g., antibiotics, pharmaceuticals like Artemisinin, anticancer agents like Taxol (paclitaxel) among others)
have been produced by organisms that are not optimal for industrial production. Although some of these natural
products can be chemically synthesized, the complex structures of several of these compounds makes chemical
synthesis difficult and commercially infeasible. As a result, there is increasing need to develop sustainable and
readily tractable technological platforms to synthesize these drugs and pharmaceutical intermediates. The
central objective of this proposal is to develop a sustainable technological platform that harnesses light energy
and biocatalysis to synthesize molecules of significant relevance to human life. We envision doing this by
establishing cyanobacterial endosymbionts within yeasts cells, such that the endosymbiotic cyanobacteria
provide ATP and assimilated carbon (generated from photosynthesis) to the yeast cells, which utilize it to produce
biologically important natural products. This platform will allow us to couple the remarkable biosynthetic and
biocatalytic potential of yeast to the photosynthetic ability of cyanobacteria to develop a sustainable and simple
bioproduction platform to produce natural products of significant value to human life (vide infra). Premise: (i)
Saccharomyces cerevisiae has been recently harnessed to produce high titers of biologically important
molecules such as amorphadiene and artemisinic acid, (precursors to Artemisinin) and taxadiene (a key
precursor to Taxol), (ii) we had previously developed model endosymbiosis between S. cerevisiae /E. coli to
study mitochondrial evolution are currently engineering yeast/cyanobacteria endosymbiosis (preliminary data in
Specific Aim 1) and (iii) our preliminary data on engineering model yeast/cyanobacteria endosymbiosis.
 In this proposal, we will focus on three key areas: (i) We have engineered experimental platform to
establish endosymbiosis between model cyanobacteria, Synechococcus elongatus, and model budding yeast,
S. cerevisiae. We will expand this platform by engineering novel cyanobacterial mutants as putative
endosymbionts. We will extensively characterize the engineered yeast/cyanobacteria endosymbiosis to develop
strategies to improve their stability, growth rate and homogeneity. (ii) We will create a metabolite-driven synthetic
communication system to control endosymbiosis and optimize our platform for metabolic engineering. (iii) We
will utilize our photosynthetic endosymbiotic platform to produce key precursors of FDA approved compounds,
Artemisinin and Taxol. These studies will be the first step towards our long-term goal of developing a
photosynthetic and genetically tractable endosymbiotic platf...

## Key facts

- **NIH application ID:** 10491963
- **Project number:** 5R01GM139949-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Angad Mehta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $295,069
- **Award type:** 5
- **Project period:** 2021-09-20 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491963

## Citation

> US National Institutes of Health, RePORTER application 10491963, Harnessing light and model endosymbiosis to produce natural products (5R01GM139949-02). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10491963. Licensed CC0.

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