Dow Global Technolgoies LLC

Paresh C Sanghani

Eric C Shiue

Scott A Greenwalt

Christopher C Stowers

Brandon A Rodriguez

Sarah Delaplane

Prakash Bhosale

Amudhan Venkateswaran

Genetically modified isopropylmalate isomerase enzyme complexes (e.g., LeuCD′ enzyme complexes), microbial organisms including genetically modified isopropylmalate isomerase enzyme complexes (e.g., LeuCD′), and processes for preparing C7-C11 2-ketoacids with genetically modified isopropylmalate isomerase enzyme complexes (e.g., LeuCD′). The genetically modified isopropylmalate isomerase enzyme complexes (e.g., LeuCD′ enzyme complexes), microbial organisms, and processes for preparing C7-C11 2-ketoacids can be used to produce C6-C10 aldehydes, alkanes, alcohols, and carboxylic acids, both in vivo and in vitro.

Genetically modified isopropylmalate isomerase enzyme complexes and processes to prepare elongated 2-ketoacids and C5-C10 compounds therewith

Genetically modified LeuCD' enzyme complexes, processes for preparing a C-C2-ketoacid utilizing genetically modified LeuCD&#x2032; enzyme complexes, and microbial organisms including modified LeuCD enzyme complexes are described. The instantly-disclosed genetically modified LeuCD&#x2032; enzyme complexes, processes for preparing a C-C2-ketoacid, and microbial organisms including modified LeuCD&#x2032; enzyme complexes can be particularly useful for producing C-Caldehydes, alkanes, alcohols, and carboxylic acids, both in vivo and in vitro.

Process to prepare elongated 2-ketoacids and C-5-C10 compounds therefrom via genetic modifications to microbial metabolic pathways

Genetically modified isopropylmalate isomerase enzyme complexes (e.g., LeuCD' enzyme complexes), microbial organisms including genetically modified isopropylmalate isomerase enzyme complexes (e.g., LeuCD&#x2032;), and processes for preparing C-C2-ketoacids with genetically modified isopropylmalate isomerase enzyme complexes (e.g., LeuCD&#x2032;). The genetically modified isopropylmalate isomerase enzyme complexes (e.g., LeuCD&#x2032; enzyme complexes), microbial organisms, and processes for preparing C-C2-ketoacids can be used to produce C-Caldehydes, alkanes, alcohols, and carboxylic acids, both in vivo and in vitro.

Genetically modified isopropylmalate isomerase enzyme complexes and processes to prepare elongated 2-ketoacids and C-Ccompounds therewith

Genetically modified isopropylmalate synthases, processes for preparing a C-C2-ketoacids utilizing genetically modified isopropylmalate synthases, and microbial organisms including genetically modified isopropylmalate synthases are described. The genetically modified isopropylmalate synthases, processes for preparing a C-C2-ketoacids, and microbial organisms including genetically modified isopropylmalate synthases can be particularly useful for producing corresponding Caldehydes, alcohols, carboxylic acids, and Calkanes both in vivo and in vitro.

Processes to prepare elongated 2-ketoacids and C5-C10 compounds therefrom via genetic modifications to microbial metabolic pathways

Modification of the amino acid sequence of a phenylpyruvate decarboxylase fromproduces a novel group of phenylpyruvate decarboxylases with improved specificity to certain substrates, including in particular C7-C11 2-ketoacids such as, for example, 2-ketononanoate and 2-keto-octanoate. This specificity enables effective use of the phenylpyruvate decarboxylase in, for example, an in vivo process wherein 2-ketobutyrate or 2-ketoisovalerate are converted to C7-C11 2-ketoacids, and the novel phenylpyruvate decarboxylase converts the C7-C11 2-ketoacid to a C6-C10 aldehyde having one less carbon than the 2-ketoacid. Ultimately, through contact with additional enzymes, such C6-C10 aldehydes may be converted to, for example, C6-C10 alcohols, C6-C10 carboxylic acids, C6-C10 alkanes, and other derivatives. Use of the novel genetically modified phenylpyruvate decarboxylases may represent a lower cost alternative to non-biobased approaches.

Genetically modified phenylpyruvate decarboxylase, processes to prepare, and uses thereof

Modification of metabolic pathways includes genetically engineering at least one enzyme involved in elongating 2-ketoacids during leucine biosynthesis, and preferably at least isopropylmalate dehydrogenase or synthase (LeuB or LeuA in), to include at least such non-native enzyme, enzyme complex, or combination thereof to convert 2-ketobutyrate or 2-ketoisovalerate to a C7-C11 2-ketoacid, wherein the production of such is at a higher efficiency than if a purely native pathway is followed. The C7-C11 2-ketoacid may then be converted, via a native or genetically engineered thiamin dependent decarboxylase, to form a C6-C10 aldehyde having one less carbon than the C7-C11 2-ketoacid being converted. In some embodiments the C6-C10 aldehyde may then be converted via additional native or genetically engineered enzymes to form other C6-C10 products, including alcohols, carboxylic acids, and alkanes. This genetic engineering offers the opportunity for commercial scale of in vivo biosynthetic processes that may be more cost-efficient than non-biobased approaches to produce the same products.

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Indianapolis, IN, United States of America

Paresh C Sanghani