# Connecting social interactions to natural product biosynthesis in actinomycete bacteria

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $319,159

## Abstract

PROJECT SUMMARY/ABSTRACT
 Natural products from bacteria have long been the frontline defense in the struggle against bacterial
infections, and have also found wide use as antifungals, anthelminthics, anti-cancer drugs, and
immunosupressants. One group of bacteria, the actinomycetes, has historically been the deepest source of
clinically-useful natural products. Recent work has demonstrated that natural product biosynthesis often results
from microbial communication in the form of interactions between cells in colonies of a single actinomycete, or
by interactions with microbes of different species. Together, these observations underscore the idea that
induction of natural product biosynthesis is socially-driven. The goal of this study is to understand how inter- and
intra- species interactions activate natural product biosynthesis at a molecular level. Our first research objective
seeks a mechanistic understanding of how a model actinomycete, Streptomyces coelicolor, activates expression
of genes for natural product biosynthesis in the presence of other actinomycetes. We have found that this
activation requires an unusual and poorly-understood signal transduction mechanism found in actinomycetes
that shares parallels with eukaryotic systems that rely on G protein activation. Our second research objective
seeks a systems-level understanding of natural product biosynthesis in S. coelicolor within the context of cell
fate decisions. Knowledge generated from this objective may be employed to someday manipulate cell fates
within actinomycete cultures to drive natural products discovery and production. These objectives run in parallel
with our efforts to build a microfluidic device for studying microbial interspecies interactions with unprecedented
speed, throughput, and specificity. This device will have multiple applications related to our first two objectives
and beyond. This research will illuminate the social aspect of natural product biosynthesis, and in the long term,
provide a foundation for harnessing microbial social cues and genetic regulation to maximize future natural
products discovery efforts.
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## Key facts

- **NIH application ID:** 10451652
- **Project number:** 5R35GM128849-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Matthew F Traxler
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $319,159
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10451652

## Citation

> US National Institutes of Health, RePORTER application 10451652, Connecting social interactions to natural product biosynthesis in actinomycete bacteria (5R35GM128849-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10451652. Licensed CC0.

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