Enhanced production of fatty acid derivatives

Abstract

Genetically engineered cells and microorganisms are provided that produce fatty alcohols from the fatty acid biosynthetic pathway, as well as methods of their use.

1 - 18 . (canceled) 
     
     
         19 . A genetically modified bacterial cell for production of a fatty alcohol, comprising an exogenous nucleic acid sequence encoding a fatty acid derivative enzyme comprising an acyl-CoA reductase, wherein said bacterial cell converts a carbon source into a fatty alcohol. 
     
     
         20 . The bacterial cell of  claim 19 , wherein said acyl-CoA reductase is encoded by a gene selected from the group consisting of acr1, acrM, BmFAR, mFAR1, and mFAR2. 
     
     
         21 . The bacterial cell of  claim 20 , wherein said acyl-CoA reductase is encoded by said acr1 gene from  Acinetobacter baylyi  ADP1. 
     
     
         22 . The bacterial cell of  claim 20 , wherein said acyl-CoA reductase is encoded by said acrM gene from  Acinetobacter  sp. M1. 
     
     
         23 . The bacterial cell of  claim 20 , wherein said acyl-CoA reductase is encoded by said BmFAR gene from  Bombyx mori.    
     
     
         24 . The bacterial cell of  claim 20 , wherein said acyl-CoA reductase is encoded by said mFAR1 gene from  Mus musculus.    
     
     
         25 . The bacterial cell of  claim 20 , wherein said acyl-CoA reductase is encoded by said mFAR2 gene from  Mus musculus.    
     
     
         26 . The bacterial cell of  claim 19 , wherein said cell is further genetically modified to express an exogenous nucleic acid sequence encoding an acyl-CoA synthase. 
     
     
         27 . The bacterial cell of  claim 26 , wherein said acyl-CoA synthase is encoded by a gene selected from the group consisting of fadD, fadDD35, yhfL, fadD1, fadD2, fadDD22, fadK, and faa3p. 
     
     
         28 . The bacterial cell of  claim 27 , wherein said acyl-CoA synthase is encoded by said fadD gene from  Escherichia coli.    
     
     
         29 . The bacterial cell of  claim 27 , wherein said acyl-CoA synthase is encoded by said fadDD35 gene from  Mycobacterium tuberculosis  HR7Rv. 
     
     
         30 . The bacterial cell of  claim 27 , wherein said acyl-CoA synthase is encoded by said yhfL gene from  Bacillus subtilis.    
     
     
         31 . The bacterial cell of  claim 27 , wherein said acyl-CoA synthase is encoded by said fadD1 gene from  Pseudomonas aeruginosa.    
     
     
         32 . The bacterial cell of  claim 27 , wherein said acyl-CoA synthase is encoded by said fadD2 gene from  Pseudomonas aeruginosa  PAO1. 
     
     
         33 . The bacterial cell of  claim 27 , wherein said acyl-CoA synthase is encoded by said fadDD22 gene from  Mycobacterium tuberculosis  HR7Rv. 
     
     
         34 . The bacterial cell of  claim 27 , wherein said acyl-CoA synthase is encoded by said fadK gene from  Escherichia coli.    
     
     
         35 . The bacterial cell of  claim 27 , wherein said acyl-CoA synthase is encoded by said faa3p gene from  Saccharomyces cerevisiae.    
     
     
         36 . The bacterial cell of  claim 26 , wherein said cell is further genetically modified to express an exogenous nucleic acid sequence encoding a thioesterase. 
     
     
         37 . The bacterial cell of  claim 36 , wherein said thioesterase is encoded by a gene selected from the group consisting of tesA, ′tesA, tesB, fatB, fatB1, fatB2, fatB3, fatA, and fatA1. 
     
     
         38 . The bacterial cell of  claim 37 , wherein said thioestrase is encoded by said tesA gene from  Escherichia coli.    
     
     
         39 . The bacterial cell of  claim 37 , wherein said thioestrase is encoded by said ′tesA gene from  Escherichia coli.    
     
     
         40 . The bacterial cell of  claim 37 , wherein said thioestrase is encoded by said tesB gene from  Escherichia coli.    
     
     
         41 . The bacterial cell of  claim 37 , wherein said thioestrase is encoded by said fatB gene from  Cinnamonum camphorum, Umbellularia californica , or  Arabidopsis thaliana.    
     
     
         42 . The bacterial cell of  claim 37 , wherein said thioestrase is encoded by said fatB1 gene from  Umbellularia californica.    
     
     
         43 . The bacterial cell of  claim 37 , wherein said thioestrase is encoded by said fatB2 gene from  Cuphea hookeriana.    
     
     
         44 . The bacterial cell of  claim 37 , wherein said thioestrase is encoded by said fatB3 gene from  Cuphea hookeriana.    
     
     
         45 . The bacterial cell of  claim 37 , wherein said thioestrase is encoded by said fatA gene from  Arabidopsis thaliana, Bradyrhiizobium japonicum , or  Cuphea hookeriana.    
     
     
         46 . The bacterial cell of  claim 37 , wherein said thioestrase is encoded by said fatA1 gene from  Helianthus annus.    
     
     
         47 . The bacterial cell of  claim 36 , wherein said cell is further genetically modified to express an exogenous nucleic acid sequence encoding an acetyl-CoA carboxylase. 
     
     
         48 . The bacterial cell of  claim 47 , wherein said acetyl-CoA carboxylase is encoded by a gene selected from the group consisting of  Escherichia coli, Desulfovibrio desulfuricans, Erwinia  ( micrococcus )  amylovora, Kineococcus radiotolerans  SRS30216 , Rhodospirillum rubrum , and  Vibrio furnissii.    
     
     
         49 . The bacterial cell of  claim 19 , wherein said bacterial cell is an  Escherichia coli  cell. 
     
     
         50 . The bacterial cell of  claim 19 , wherein the fatty alcohol is released into a fermentation media. 
     
     
         51 . The bacterial cell of  claim 50 , wherein the fermentation media comprises one or more of C8, C10, C12, C14, C16 and C18 fatty alcohols. 
     
     
         52 . The bacterial cell of  claim 50 , wherein the fermentation media comprises unsaturated fatty alcohols. 
     
     
         53 . The bacterial cell of  claim 50 , wherein the fermentation media comprises saturated fatty alcohols. 
     
     
         54 . The bacterial cell of  claim 50 , wherein the fermentation media comprises straight chain fatty alcohols. 
     
     
         55 . The bacterial cell of  claim 50 , wherein the fermentation media comprises branched chain fatty alcohols. 
     
     
         56 . A genetically modified bacterial cell for production of a fatty alcohol, comprising an exogenous nucleic acid sequence encoding a fatty acid derivative enzyme comprising an acyl-CoA reductase and an acyl-CoA synthase, wherein said bacterial cell converts a carbon source into a fatty alcohol. 
     
     
         57 . The bacterial cell of  claim 56 , wherein said acyl-CoA reductase is encoded by an acr1 gene from  Acinetobacter baylyi  ADP1, and wherein said acyl-CoA synthase is encoded by a fadD gene from  Escherichia coli.    
     
     
         58 . The bacterial cell of  claim 56 , wherein said cell is further genetically modified to express an exogenous nucleic acid sequence encoding a thioesterase. 
     
     
         59 . The bacterial cell of  claim 58 , wherein said thioesterase is encoded by a ′tesA gene from  Escherichia coli.    
     
     
         60 . A genetically modified bacterial cell for production of a fatty alcohol, comprising an exogenous nucleic acid sequence encoding a fatty acid derivative enzyme comprising an acyl-CoA reductase, an acyl-CoA synthase, and a thioesterase, wherein said bacterial cell converts a carbon source into a fatty alcohol. 
     
     
         61 . The bacterial cell of  claim 60 , wherein said acyl-CoA reductase is encoded by an acr1 gene from  Acinetobacter baylyi  ADP1, wherein said acyl-CoA synthase is encoded by a fadD gene from  Escherichia coli , and wherein said thioesterase is encoded by a ′tesA gene from  Escherichia coli.