# Generating an Actinobacterial Chassis for Antimicrobial Discovery

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $23,102

## Abstract

Abstract
Natural products have long been the primary resource as scaffolds for therapeutic drugs, particularly against
the threat of antimicrobial resistance. Once dormant, the field of natural product discovery is experiencing
a renaissance as advancements in the field of metagenomics has allowed the investigation of a vast,
untapped reservoirs of gene clusters. Large environmental DNA (eDNA) segments, previously inaccessible
due to lack of cultivability in the host, are now routinely constructed on broad-host vectors and shuttled
into heterologous hosts, primarily E. coli and S. lividans. Antimicrobial compounds are discovered through
high-throughput screens of eDNA in these host vectors, but are limited by very low ‘hit rates’. Heterologous
hosts often do not have or poorly express the transcriptional recognition elements, alternative sigma factors,
that guide the host RNA polymerase that can activate these biosynthetic gene clusters (BGCs). This
proposal outlines the development of a broad-based chassis organism for activation of BGCs from
actinobacteria, the organisms responsible for the majority of antimicrobials. Alternative sigma factors most
commonly found in actinobacteria will be combinatorially expressed in Pseudomonas putida, an organism
that is both genetically tractable like E. coli and has a high-GC content organism with significant tolerance
to xenobiotics like S. lividans. Through an interdisciplinary approach combining insights from
microbiology, synthetic biology and analytical chemistry, this proposal seeks to provide a system that will
increase the ‘hit rate’ in genome mining, which will be an important tool to the broader scientific
community.

## Key facts

- **NIH application ID:** 10213542
- **Project number:** 3F32GM125179-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Amin Zargar
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $23,102
- **Award type:** 3
- **Project period:** 2018-08-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213542

## Citation

> US National Institutes of Health, RePORTER application 10213542, Generating an Actinobacterial Chassis for Antimicrobial Discovery (3F32GM125179-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10213542. Licensed CC0.

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