The broad objective of the proposal is to test whether E. coli hosts genetically altered to support complex natural product biosynthesis improve the success of screening environmental DNA libraries for novel and useful antibiotics and consists of the following Specific Aims: (1) To further modify both the E. coli strains engineered to produce polyketides and non-ribosomal peptides, and our BAC vector in which libraries are constructed, to allow screening of large- insert environmental DNA BAC clones in both single and multiple copy number; (2) To construct an environmental library in the modified BAC vector and to screen for antibiotic activity from environmental DNA libraries, in both low and high copy, transferred to native and genetically modified E. coli hosts.
In Specific Aim 1, both the E. coli strains currently used for complex natural product production and the vector system used for high-throughput environmental DNA antibiotic screening will be modified and made compatible for efforts to integrate these advanced E. coli heterologous hosts into environmental DNA screening schemes.
Aim 2 will then test for advanced antibiotic screening success based upon use of advanced E. coli heterologous hosts. Success will point to a new level of accessibility to as- yet-undiscovered antibiotic agents. ? ? Success will provide new antibiotic compounds to be used in the continual battle against antibiotic-resistant bacteria. More broadly, a method will be developed to access more chemically diverse natural products (antibiotics, anticancer agents, immunosuppressants, or others) from previously inaccessible terrestrial and marine natural environments. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43AI074224-01
Application #
7273794
Study Section
Special Emphasis Panel (ZRG1-IDM-Q (10))
Program Officer
Korpela, Jukka K
Project Start
2007-09-15
Project End
2009-08-31
Budget Start
2007-09-15
Budget End
2009-08-31
Support Year
1
Fiscal Year
2007
Total Cost
$198,047
Indirect Cost
Name
Earthgenes Pharmaceuticals, LLC.
Department
Type
DUNS #
170718881
City
Lexington
State
MA
Country
United States
Zip Code
02421