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Abstract

Grant Number:	1R01GM075857-01
Project Title:	Platforms for nonribosomal peptide manipulation(RMI)

PI Information:	Name	Email	Title
	WANG, CLAY C.	clayw@usc.edu	ASSISTANT PROFESSOR

Abstract: DESCRIPTION (provided by applicant): The goal of this three year proposal is to develop E. coli as an efficient heterologous expression system for the DNA bisintercalator triostin. A non-ribosomally synthesized peptide, triostin is a known antibiotic and anticancer agent. We will test the hypothesis that by metabolically engineering the E. coli host, modifying the plasmid vector, and altering the triostin gene, triostin and its analogs could be biosynthesized. There are two specific aims for this research, (1) Metabolically engineer E. coli to produce triostin. (2) Modify the triostin NRPS to produce analogs with altered sequence specificity and selectivity. Preliminary results. We have identified a four module non-ribosomal peptide synthetase that contains adenylation domains specific for Serine, Alanine, Cysteine, Valine amino acids (the four amino acids found in triostin.) The significance of this research is that it will (a) improve the mechanistic understanding of the assembly of C2-symmetric non-ribosomal peptides, (b) provide a general host for the expression of diverse non-ribosomal peptide synthetase genes.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
bacterial genetics, gene expression, genetic manipulation, synthetic peptide
Escherichia coli, analog, biotherapeutic agent, transfection /expression vector
biotechnology

Institution:	UNIVERSITY OF SOUTHERN CALIFORNIA
	DEPARTMENT OF CONTRACTS AND GRANTS
	LOS ANGELES, CA 90033
Fiscal Year:	2005
Department:	PHARMACOLOGY AND PHARMACEUTICAL SCIS
Project Start:	23-SEP-2005
Project End:	31-JUL-2008
ICD:	NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
IRG:	ZRG1

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