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San Diego, CA, United States

Fermentation of carbohydrate substrates by microorganisms represents an attractive route for the manufacture of industrial chemicals from renewable resources. The technology to manipulate metabolism of bacteria and yeast, including the introduction of heterologous chemical pathways, has accelerated research in this field. However, the public literature contains very few examples of strains achieving the production metrics required for commercialization. This article presents the challenges in reaching commercial titer, yield, and productivity targets, along with other necessary strain and process characteristics. It then reviews various methods in systems biology, synthetic biology, enzyme engineering, and fermentation engineering which can be applied to strain improvement, and presents a strategy for using these tools to overcome the major hurdles on the path to commercialization. © 2013 Elsevier Ltd. Source


The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or -ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB). Also provided is a non-naturally occurring microbial biocatalyst including a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways include at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-butyrate kinase, phosphotransbutyrylase, -ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce 1,4-butanediol (BDO). Additionally provided are methods for the production of 4-HB and BDO.


Patent
Genomatica | Date: 2015-04-29

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. The invention additionally provides methods of using such microbial organisms to produce BDO.


A non-naturally occurring eukaryotic or prokaryotic organism includes one or more gene disruptions occurring in genes encoding enzymes imparting increased fumarate, malate or acrylate production in the organism when the gene disruption reduces an activity of the enzyme. The one or more gene disruptions confers increased production of acrylate onto the organism. Organisms that produce acrylate have an acrylate pathway that at least one exogenous nucleic acid encoding an acrylate pathway enzyme expressed in a sufficient amount to produce acrylate, the acrylate pathway comprising a decarboxylase. Methods of producing fumarate, malate or acrylate include culturing these organisms.


Patent
Genomatica | Date: 2015-03-20

A non-naturally occurring microbial organism having an aniline pathway includes at least one exogenous nucleic acid encoding an aniline pathway enzyme expressed in a sufficient amount to produce aniline.

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