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Cell free Expression of Cryptic Actinomycetes Gene Clusters for Natural Products Discovery

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43AT009522-01
Agency Tracking Number: R43AT009522
Amount: $225,000.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: R
Solicitation Number: PA16-341
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-04-01
Award End Date (Contract End Date): 2018-09-30
Small Business Information
San Francisco, CA 94107-3007
United States
DUNS: 079761816
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (646) 725-6686
Business Contact
Phone: (646) 725-6686
Research Institution

Project Summary
Microbial natural products are known to be rich resources for the search of drug candidates Advances in next
generation sequencing have exponentially increased the metagenomic data available from actinomycetes
which are known to be prolific producers of bioactive secondary metabolites However much of natural product
chemical diversity has not been explored using traditional cultivation dependent strategies Furthermore a
significant fraction of gene clusters from cultivated microbial sources remain silent under standard fermentation
conditions In theory heterologous expression of natural product gene clusters can provide access to chemical
diversity from both uncultivated organisms and cryptic pathways However current cell based heterologous
expression approach remains to be the biggest bottleneck for genomic mining as often times it can be very
time consuming and expensive and usually limited to a small number of standard hosts
In Phase I will this bottleneck by applying our cell free expression technology to heterologously express cryptic
actinomycete gene clusters in vitro Cryptic biosynthetic gene clusters of natural products with therapeutic
value can be characterized in a high throughput and cost effective fashion We propose to achieve this
objective through three specific aims Aim Platform development of diverse actinomycetes cell free systems
We anticipate that cell free systems from multiple actinomycete strains will improve the probability of cryptic
cluster heterologous expression Aim Identification of cryptic actinomycetes biosynthetic pathways of natural
products We will identify never before expressed cryptic actinomycetes biosynthetic pathways and filter based
on expression potential in our cell free expression platform Aim High throughput in vitro cell free
expression We will run high throughput experiments to then express and characterize unique cryptic
gene clusters
If successful this valuable platform can be used to activate the pool of bioinformatically available cryptic
biosynthetic gene clusters for the discovery of new natural products from actinomycetes with high
pharmacological value Phase II efforts will focus on platform scale up and the identification and scaling of
potential therapeutic candidates for downstream characterization Project Narrative
Natural products remain a valuable resource for novel therapeutics to address human health This proposal uses
cell free expression systems as an alternative method to search for novel natural products from actinomycetes
By being able to express cryptic gene clusters without the use of cells we hope to exponentially increase the
rate of rediscovery of natural products as a reservoir for therapeutics

* Information listed above is at the time of submission. *

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