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(12) United States Patent (10) Patent No.: US 8,945,859 B2 Donaldson Et Al

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(12) United States Patent (10) Patent No.: US 8,945,859 B2 Donaldson Et Al USOO8945859B2 (12) United States Patent (10) Patent No.: US 8,945,859 B2 Donaldson et al. (45) Date of Patent: Feb. 3, 2015 (54) PRODUCTION OF ISOBUTANOL BY A 50/10 (2013.01); Y02E 50/343 (2013.01): CI2N MCROORGANISM WITHENHANCED 9/88 (2013.01); CI2Y 202/01006 (2013.01); ACETOLACTATE SYNTHASE ACTIVITY CI2Y 102/04004 (2013.01); C12N 15/70 (2013.01); C12N 9/0008 (2013.01): CI2N (71) Applicant: Butamax(TM) Advanced Biofuels LLC, 15/52 (2013.01); C12N 15/74 (2013.01); CI2N Wilmington, DE (US) 9/0016 (2013.01) (72) Inventors: Gail K. Donaldson, Newark, DE (US); USPC ........... 435/7.4; 435/69.1; 435/157; 435/183; Andrew C. Eliot, Wilmington, DE (US); 435/252.3; 435/320.1; 536/23.2 Dennis Flint, Newark, DE (US); Lori (58) Field of Classification Search Ann Maggio-Hall, Wilmington, DE None (US); Vasantha Nagarajan, See application file for complete search history. Wilmington, DE (US) (56) References Cited (73) Assignee: Butamax Advanced Biofuels LLC, U.S. PATENT DOCUMENTS Wilmington, DE (US) 4.424,275 A 1/1984 Levy 4,568,643 A 2/1986 Levy (*) Notice: Subject to any disclaimer, the term of this 5,210,032 A 5/1993 Kashket patent is extended or adjusted under 35 5,210,296 A 5/1993 Cockrem et al. U.S.C. 154(b) by 0 days. 5,686,276 A 11/1997 Laffendet al. 6,013,494. A 1/2000 Nakamura et al. (21) Appl. No.: 13/839,246 6,177.264 B1 1/2001 Eggeling et al. 6,358,717 B1 3/2002 Blaschek et al. 6,579,330 B2 6/2003 Nakahama et al. (22) Filed: Mar 15, 2013 6,660,507 B2 12/2003 Cheng et al. 6,787,334 B1 9, 2004 Elischweski et al. (65) Prior Publication Data 7,632,663 B1 12/2009 Eggeling et al. 7.851,188 B2 * 12/2010 Donaldson et al. ........... 435,160 US 2014/OO3O794 A1 Jan. 30, 2014 7.993,889 B1 8/2011 Donaldson et al. 8,017,375 B2 9, 2011 Feldman et al. 8, 178,328 B2 5/2012 Donaldson et al. Related U.S. Application Data 8,273,558 B2 9/2012 Donaldson et al. 8,283,144 B2 * 10/2012 Donaldson et al. ........... 435,160 (63) Continuation of application No. 13/646,097, filed on 8,735,114 B2 5/2014 Donaldson et al. Oct. 5, 2012, which is a continuation of application 2002/00284.92 A1 3/2002 Lenke et al. No. 12/939,284, filed on Nov. 4, 2010, now Pat. No. 2004/0146996 A1 7/2004 Yocum et al. 8.283,144, which is a continuation of application No. 2004/O157301 A1 8, 2004 Chotani et al. 1 1/586,315, filed on Oct. 25, 2006, now Pat. No. 2009,0081746 A1 3/2009 Liao et al. 7,851,188. 2009, 0226991 A1 9, 2009 Feldman et al. (60) Provisional application No. 60/730,290, filed on Oct. (Continued) 26, 2005. FOREIGN PATENT DOCUMENTS (51) Int. Cl. AU 620802 B2 10, 1988 GOIN 33/573 (2006.01) CA 2O39.245 3, 1991 CI2P2/06 (2006.01) (Continued) CI2P 7/04 (2006.01) CI2N 9/00 (2006.01) OTHER PUBLICATIONS CI2N L/20 (2006.01) CI2N I/00 (2006.01) Wynn et al. J. Biol Chem. Jun. 25, 1992:267(18): 12400-3.* Bekkaoui. F., et al., “Isolation and structure of an acetolactate CI2N IS/00 (2006.01) Synthase gene from Schizosaccharomyces pombe and completion of C7H 2L/04 (2006.01) the ilv2 mutation in Saccharomyces cerevisiae, " Current Genetics CI2N 9/10 (2006.01) 24:544-547, Springer-Verlag, Germany 1993. CI2N 15/75 (2006.01) Card, J.C. and Farrell, L.M., “Separation of Alcohol-Water Mixtures CI2N 9/04 (2006.01) Using Salts' in Technical Reports of Oak Ridge National Laboratory, CI2N 15/8 (2006.01) Chemical Technology Division, Contract No. W-7405-eng-26, 1982. CI2P 7/16 (2006.01) (Continued) CI2N 9/88 (2006.01) CI2N 15/70 (2006.01) CI2N 9/02 (2006.01) Primary Examiner — Christian Fronda CI2N 15/52 (2006.01) (57) ABSTRACT CI2N 15/74 (2006.01) Methods for the fermentative production of four carbon alco CI2N 9/06 (2006.01) hols is provided. Specifically, butanol, preferably isobutanol (52) U.S. Cl. is produced by the fermentative growth of a recombinant CPC .............. CI2N 15/81 (2013.01); C12N 9/1096 bacterium expressing an isobutanol biosynthetic pathway. (2013.01); C12N 15/75 (2013.01); C12N 9/0006 (2013.01); CI2P 7/16 (2013.01); Y02E 17 Claims, 1 Drawing Sheet US 8,945,859 B2 Page 2 (56) References Cited Radmacher, E., et al., “Linking Central Metabolism with Increased Pathway Flux: L-Valine Accumulation by Corynebacterium U.S. PATENT DOCUMENTS glutamicum, "App Environ. Micro. 68:2246-2250, American Society for Microbiology, United States, 1993. 2009/0305363 A1 12/2009 Anthony et al. 2010.0081182 A1 4/2010 Paul et al. Renna, M.C., et al., “Regulation of the Bacillus subtilis als.S, alsD, 2010, 0120105 A1 5/2010 Anthony et al. and alsR Genes Involved in Post-Exponential-Phase Production of 2010/0129886 A1 5/2010 Anthony et al. Acetoin.” J. Bacteriology 175:3863-3875, American Society for 2010, O151545 A1 6, 2010 Roessler et al. Microbiology, United States, 1993. 2011/0053235 A1 3/2011 Festel et al. Rosenfield, E. and Beauvoit, B., “Role of the non-respiratory path 2011/011 1472 A1 5/2011 Donaldson et al. ways in the utilization of molecular oxygen by Saccharomyces 2011 0112334 A1 5/2011 Donaldson et al. cerevisiae," Yeast 20:1115-1144. John Wiley & Sons, Inc., United 2011 0160442 A1 6/2011 Pietarinen et al. 2011/0313206 A1 12/2011 Donaldson et al. States, 2003. 2013/0171706 A1 7/2013 Donaldson et al. Screen capture of http://enzyme...expasy.org/EC/2.2.1.6, the ExPASy. 2013,0183731 A1 7/2013 Donaldson et al. Bioformatics Resource Portal Enzyme Nomenclature Database for 2014/0051151 A1 2/2014 Donaldson et al. EC No. 2.2.1.6. ExPASy Proteomics Server retrieved on Aug. 16. 2011. FOREIGN PATENT DOCUMENTS Screen capture of http://www.chem.qmul.ac.uk/iubmb? enzyme? EC2/2/1/6.html, the IUBMB Enzyme Nomenclature Database for EP O 112 459 A1 T 1984 EC No. 2.2.1.6, retrieved on Sep. 12, 2011. EP O 282474 A1 9, 1988 Smit, Ph.D. Thesis, Wageningen Universiteit (Wageningen, The EP O 315949 A2 5, 1989 EP 1 1499.18 A1 10, 2001 Netherlands), Formation of Amino Acid Derived Cheese Flavour JP 61-209594 9, 1986 Compounds, orally defended on Apr. 23, 2004, cataloged into the JP 63-017695 1, 1988 U.S.D.A. National Agricultural Library system on Oct. 3, 2004. JP 63-102687 5, 1988 Catalog Receipt from U.S.D. A. National Agricultural Library of JP 63-254986 10, 1988 Smit, Ph.D. Thesis, Wageningen Universiteit (Wageningen, The JP 2000-41655 A 2, 2000 Netherlands), Formation of Amino Acid Derived Cheese Flavour WO WO 90/02193 A1 3, 1990 Compounds, MARC Record View, 2 pages, indicating date cataloged WO WO 98.51813 A1 11, 1998 as 2004 1003 (i.e. Oct. 3, 2004) via MARC Code “005”. WO WOOOf 50624 A1 8, 2000 Re-examination Request Control No. 95/001.718, filed on Aug. 18. WO WOO1,21772 A2 3, 2001 2011. WO WO 2008/072920 A1 6, 2008 Re-examination Request Control No. 95/001.735, filed on Sep. 1, WO WO 2008/072921 A1 6, 2008 2011. OTHER PUBLICATIONS Complaint filed on Jan. 14, 2011 by Plaintiff ButamaxTM Advanced Biofuels LLC against Defendant Gevo, Inc. in the United States District Court for the District of Delaware, Case 1:1 1-cv-00054 Derrick, S. and Large, P., “Activities of the enzymes of the Ehrlich SRL-MPT. Pathway and formation of branched-chain alcohols in Sac Answer to Complaint filed on Mar. 25, 2011 by Defendant Gevo, Inc. charomyces cervisiae and Candida utilis grown in continous culuture in the United States District Court for District of Delaware, Case on valine or ammonium as sole nitrogen source. J. of General 1:11-cv-00054-SRL-MPT. Microbiology 139:2783-2792, Society for Chemical Microbiology, Amended Complaint filed on Aug. 11, 2011 by Plaintiff ButamaxTM Great Britain, 1993. against Defendant Gevo, Inc. in the United States District Court for Dickinson, J.R., et al., “An Investigation of the Metabolism of Valine the District of Delaware, Case 1:1 1-cv-00054-SRL-MPT. to Isobutyl Alcohol in Saccharomyces cerevisiae,” J. Biol. Chem. Answer to Amended Complaint filed on Sep. 13, 2011 by Defendant Gevo, Inc. in the United States District Court for the District of 273(40): 25751-25756, The American Society for Biochemistry and Delaware, Case 1:1 1-cv-00054-SRL-MPT. Molecular Biology, Inc., United States, 1998. Plaintiff's Opening Brief in Support of its Motion for a Preliminary Dickinson, J.R., et al., “The Catabolism of Amino Acids to Long Injunction (Reduced Version) filed on Sep. 30, 2011 in the United Chain and Complex Alcohols in Saccharomyces cerevisiae, "J. Biol. States District Court for the District of Delaware, Case 1:1 1-cv Chem. 278:8028-8034. The American Society for Biochemistry and OOO54-SRL-MPT. Molecular Biology, Inc., United States, 2003. Atsumi, S., et al., "Acetolactate synthase from Bacillus subtilis serves Hansen, J., et al., Topics in Current Genetics, Chapter, 5, vol. 2, J.H. as a 2-ketoisovalerate decarboxylase for isobutanol biosynthesis in de Winde (Ed.): Functional Genetics of Industrial Yeasts, Springer Escherichia coli, 'Appl.
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