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Characterization of a low mutation rate E. coli in extended fermentation

Award Number: R44GM105177
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2013
PERIOD OF PERFORMANCE END DATE: 05/31/2019

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Characterization of a low mutation rate E. coli in extended fermentation - DESCRIPTION (provided by applicant): Scarab Genomics was founded to improve E coli as an industrial organism by genome engineering. These strains have stable genomes since all prophages, transposable and IS elements, and the error prone repair systems were removed. A recA- version has always been provided as an option. The goal of the Phase I project was to ascertain whether the changes already introduced are sufficient to realize extended or continuous fermentation. Data gathered in Phase I show that we have indeed supported that hypothesis. Data obtained using serial transfer with shake flasks met our criterion for production stability of 21 days, but only when the cultures were not induced. This suggested the use of a two tank system with seed and production tanks. To confirm this we performed actual fermentations using Scarab funds. The results show that stable production of a test protein, CRM197 can be extended at least 33 days with no loss of productivity. This is more than enough to justify a 10 fold lowering of the cost of production with continuous flow rather than fed batch procedures that have been used in for manufacturing in E. coli. Continuous cultures were also analyzed by DNA sequencing and this was able to detect contamination as well as mutations and rearrangements. This analysis also revealed that the Scarab strain competed well against contaminants in contrast to standard strains BL21. We are therefore proposing to take this system to the next level by developing a complete platform for continuous fermentation, called C-Flow. The FDA has recently encouraged adoption of continuous manufacturing in the pharmaceutical industry, and several large companies have recently signaled readiness to implement the change. Our aim is to attack the bottom line of E. coli fermentation by offering a simpler and cheaper process that will produce consistently higher quality bioproducts than fed batch fermentation. Our proposal is to fully characterize the C-flow system and work towards commercializing it by developing a prototype that fits in a standard 6 ft hood. One particularly useful feature will support optimization of fermentation parameters without the need to restart fermentation so the best possible performance can be quickly and inexpensively achieved by a user. Other products such as pDNA will be tested in the C-Flow system.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2017	SCARAB GENOMICS, LLC	1202 ANN ST	MADISON	WI	53713	DANE	USA	Biomedical Research and Research Training	000	3	11/16/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $864,106 )
2017	2017	SCARAB GENOMICS, LLC	1202 ANN ST	MADISON	WI	53713	DANE	USA	Biomedical Research and Research Training	000	3	6/6/2017	NON-COMPETING CONTINUATION	$864,106
														Subtotal = $864,106

Issue Date FY: 2016 ( Subtotal = $1,554,424 )
2016	2016	SCARAB GENOMICS LLC	1202 ANN STREET	MADISON	WI	53713	DANE	USA	Biomedical Research and Research Training	000	2	5/19/2016	COMPETING CONTINUATION	$1,554,424
														Subtotal = $1,554,424

Grand Total All Awards = $2,418,530

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Characterization of a low mutation rate E. coli in extended fermentation

Award Number: R44GM105177

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2013

PERIOD OF PERFORMANCE END DATE: 05/31/2019

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