Abstract:
The invention provides non-naturally occurring microbial organisms comprising a 1,4-butanediol (BDO), 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine pathway comprising at least one exogenous nucleic acid encoding a BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine pathway enzyme expressed in a sufficient amount to produce BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine and further optimized for expression of BDO. The invention additionally provides methods of using such microbial organisms to produce BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine.
Abstract:
The present invention provides a pharmaceutical composition useful for treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof, an antibacterially effective combination of a β-lactam antibiotic and an inhibitor of any bacterial peptidoglycan biosynthesis enzyme, especially GlmU, GlmU, MurA, MurB, MurC, MurD, MurE, MurF, MurG, MraY, and UppS. Further provided is a method of discovering synergists for antibiotics including: a) expressing in a cell an antisense nucleic acid against a nucleic acid encoding a gene product so as to reduce the activity or amount of the gene product in the cell, thereby producing a cell sensitized to an antibiotic; b) characterizing the sensitization of the cell to the antibiotic and selecting pairs of antibiotics and genes that result in antibiotic efficacy at one-fifth or less the concentration required in the absence of the antisense gene; c) screening for chemical compounds that inhibit the gene product corresponding to the selected synergistic gene; and d) selecting or creating chemical analogs that inhibit the gene product corresponding to the selected synergistic gene such that the inhibition occurs in the bacteria.
Abstract:
The invention provides non-naturally occurring microbial organisms comprising a 1,4-butanediol (BDO), 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine pathway comprising at least one exogenous nucleic acid encoding a BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine pathway enzyme expressed in a sufficient amount to produce BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine and further optimized for expression of BDO. The invention additionally provides methods of using such microbial organisms to produce BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine.
Abstract:
The invention provides non-naturally occurring microbial organisms comprising a 1,4-butanediol (BDO), 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine pathway comprising at least one exogenous nucleic acid encoding a BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine pathway enzyme expressed in a sufficient amount to produce BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine and further optimized for expression of BDO. The invention additionally provides methods of using such microbial organisms to produce BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine.
Abstract:
The present invention provides a pharmaceutical composition useful for treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof, an antibacterially effective combination of a β-lactam antibiotic and an inhibitor of any bacterial peptidoglycan biosynthesis enzyme, especially GlmU, GlmU, MurA, MurB, MurC, MurD, MurE, MurF, MurG, MraY, and UppS. Further provided is a method of discovering synergists for antibiotics including: a) expressing in a cell an antisense nucleic acid against a nucleic acid encoding a gene product so as to reduce the activity or amount of the gene product in the cell, thereby producing a cell sensitized to an antibiotic; b) characterizing the sensitization of the cell to the antibiotic and selecting pairs of antibiotics and genes that result in antibiotic efficacy at one-fifth or less the concentration required in the absence of the antisense gene; c) screening for chemical compounds that inhibit the gene product corresponding to the selected synergistic gene; and d) selecting or creating chemical analogs that inhibit the gene product corresponding to the selected synergistic gene such that the inhibition occurs in the bacteria.
Abstract:
The invention provides non-naturally occurring microbial organisms comprising a 1,4-butanediol (BDO) pathway comprising at least one exogenous nucleic acid encoding a BDO pathway enzyme expressed in a sufficient amount to produce BDO and further optimized for expression of BDO. The invention additionally provides methods of using such microbial organisms to produce BDO.
Abstract:
The present invention provides a pharmaceutical composition useful for treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof, an antibacterially effective combination of a β-lactam antibiotic and an inhibitor of any bacterial peptidoglycan biosynthesis enzyme, especially GlmU, GlmU, MurA, MurB, MurC, MurD, MurE, MurF, MurG, MraY, and UppS. Further provided is a method of discovering synergists for antibiotics including: a) expressing in a cell an antisense nucleic acid against a nucleic acid encoding a gene product so as to reduce the activity or amount of the gene product in the cell, thereby producing a cell sensitized to an antibiotic; b) characterizing the sensitization of the cell to the antibiotic and selecting pairs of antibiotics and genes that result in antibiotic efficacy at one-fifth or less the concentration required in the absence of the antisense gene; c) screening for chemical compounds that inhibit the gene product corresponding to the selected synergistic gene; and d) selecting or creating chemical analogs that inhibit the gene product corresponding to the selected synergistic gene such that the inhibition occurs in the bacteria.
Abstract:
The present invention provides a pharmaceutical composition useful for treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof, an antibacterially effective combination of a β-lactam antibiotic and an inhibitor of any bacterial peptidoglycan biosynthesis enzyme, especially GlmU, GlmU, MurA, MurB, MurC, MurD, MurE, MurF, MurG, MraY, and UppS. Further provided is a method of discovering synergists for antibiotics including: a) expressing in a cell an antisense nucleic acid against a nucleic acid encoding a gene product so as to reduce the activity or amount of the gene product in the cell, thereby producing a cell sensitized to an antibiotic; b) characterizing the sensitization of the cell to the antibiotic and selecting pairs of antibiotics and genes that result in antibiotic efficacy at one-fifth or less the concentration required in the absence of the antisense gene; c) screening for chemical compounds that inhibit the gene product corresponding to the selected synergistic gene; and d) selecting or creating chemical analogs that inhibit the gene product corresponding to the selected synergistic gene such that the inhibition occurs in the bacteria.
Abstract:
The invention provides non-naturally occurring microbial organisms comprising 1,4-butanediol (14-BDO) and gamma-butyrolactone (GBL) pathways comprising at least one exogenous nucleic acid encoding a 14-BDO and GBL pathway enzyme expressed in a sufficient amount to produce 14-BDO and GBL. The invention additionally provides methods of using such microbial organisms to produce 14-BDO and GBL.