Roche Vitamins Inc.

Hoffmann-La Roche Inc.

Dsm IP Assets B.v.

Dsm Nutritional Products Inc.

Other

Dsm Assets B.v.

Hoshino, Tatsuo

Tatsuo Hoshino

Masako Shinjoh

Teruhide Sugisawa

Akiko Fujiwara

Masaaki Tazoe

Yutaka Setoguchi

Akira Asakura

Kazuyuki Ojima

Noribumi Tomiyama

Tatsuya Kiyasu

Taro Miyazaki

Yoshie Nagahashi

Setsuko Ojima

Yasuhiro Furuichi

Hitoshi Kimura

Keiko Ichikawa

Yuzuru Sekine

Setsuko Masuda

Nobuo Shimma

Mitsuhiko Fujiwara

Peter Karl Matzinger

Tsutomu Kawaguchi

Shinji Kagaya

Christine Toepfer

Takahide Kon

Yoshinori Takagi

Setsuko Nomura

Setuko Ojima

Akio Fujiwara

Akifumi Noro

Yoichiro Nagatani

An object of the present invention is to provide a measure for treating or preventing a disease or condition that involves AMPK dysregulation, particularly a cancer. The present invention provides a combination therapy using a compound presented by formula (I), a pharmaceutically acceptable salt or a solvate thereof with an immune checkpoint inhibitor.

Combination therapy using ascochlorin derivative

An object of the present invention is to provide a novel ascochlorin derivative which activates adenosine monophosphate-activated protein kinase (AMPK), and is useful in the treatment or prevention of diseases or conditions that involve AMPK dysregulation. The present invention provides a compound presented by formula I, a pharmaceutically acceptable salt or a solvate thereof.

Ascochlorin derivative and use thereof as AMPK activator

The present invention relates to newly identified genes that encode proteins that are involved in the synthesis of L-ascorbic acid (hereinafter also referred to as Vitamin C). The invention also features polynucleotides comprising the full-length polynucleotide sequences of the novel genes and fragments thereof, the novel polypeptides encoded by the polynucleotides and fragments thereof, as well as their functional equivalents. The present invention also relates to the use of the polynucleotides and polypeptides as biotechnological tools in the production of Vitamin C from microorganisms, whereby a modification of the polynucleotides and/or encoded polypeptides has a direct or indirect impact on yield, production, and/or efficiency of production of the fermentation product in the microorganism. Also included are methods/processes of using the polynucleotides and modified polynucleotide sequences to transform host microorganisms. The invention also relates to genetically engineered microorganisms and their use for the direct production of Vitamin C.

Vitamin C production in a microorganism, gluconobacter

The present invention is directed to a novel cytochrome c oxidase complex, genetic materials useful for the preparation of the said complex, such as recombinant polypeptides involved in cytochrome c oxidase complex, recombinant DNA fragments, expression vectors, recombinant organisms and the like. Those novel cytochrome c oxidase complex and genetic materials may be originated from a microorganism having the identifying characteristics ofDSM 4025. The present invention also provides a method for the preparation of the said novel recombinant cytochrome c oxidase complex and a process for the production of 2-keto-L-gulonic acid (2KGA).

Cytochrome c oxidase enzyme complex

The present invention relates to a biological process for producing carotenoids utilizing a microorganism which is capable of producing carotenoids and belonging to the genus() in the presence of an inhibitor for biosynthesis of sterols from farnesyl pyrophosphate.

Process for producing carotenoids

The present invention provides a process for the production of vitamin C from a substrate, such as for instance L-sorbosone using a microorganism belonging to the genus

Microbial production of vitamin C

Disclosed is an isolated DNA encoding vitamin Bphosphate phosphatase selected from the group consisting of: (a) a DNA sequence represented in SEQ ID NO:9; (b) a DNA sequence which encodes a polypeptide having vitamin Bphosphate phosphatase activity and hybridizes under standard conditions to the DNA sequence defined in (a) or a fragment of thereof; (c) a DNA sequence which encodes a polypeptide having vitamin Bphosphate phosphatase activity, wherein said polypeptide is at least 70% identical to the amino acid sequence represented in SEQ ID NO:10; (d) a DNA sequence which encodes a polypeptide having vitamin Bphosphate phosphatase activity and is at least 70% identical to the DNA sequence represented in SEQ ID NO:9; (e) a degenerate DNA sequence of any one of (a) to (c).

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The present invention relates to a process for the production of vitamin C from L sorbosone using an aldehyde dehydrogenase which is isolated fromDSM 4025 (FERM BP-3812), said enzyme having the following physicochemical properties: (a) molecular weight of 150,000&#xb1;6,000 Da or 230,000&#xb1;9,000 Da (consisting of 2 or 3 homologous subunits, each subunit having a molecular weight of 75,000&#xb1;3,000 Da); (b) substrate specificity as active on aldehyde compounds; (c) Cofactors are pyrroloquinoline quinone and heme c; (d) Optimum pH between 6.4 and 8.2 for vitamin C production from L-sorbosone; and (e) as inhibitors Co, Cu, Fe, Ni, Zn, monoiodoacetate and ethylendiamine tetraacetic acid. The process is performed in the presence of a suitable electron acceptor and the vitamin C isolated from the reaction mixture.

Vitamin C from sorbosone

A process for producing L-ascorbic acid from 2-keto-L-gulonic acid or D-erythorbic acid from 2-keto-D-gluconic acid by contacting 2-keto-L-gulonic acid or 2-keto-D-gluconic acid, respectively, with an enzym having &#x3b1;-amylase activity in solution. The solvent for this reaction can be water, an aqueous alcohol, an organic solvent or a mixture thereof. In each case, the starting material can be in the form of the free acid, the sodium salt, or the calcium salt.

Enzymatic process for the manufacture of L-ascorbic acid and D-erythorbic acid

Disclosed is a fermentation method of astaxanthin using Phaffia rhodozyma comprising the steps of: (a) in the growing phase, feeding of a nutrient medium containing glucose or sucrose based on the specific growth rate (&#x3bc;) of Phaffia rhodozyma cells, and (b) in the astaxanthin production phase, feeding of the nutrient medium based on the astaxanthin production rate, while keeping the glucose concentration in the fermentation broth almost 0 g/L during the whole fermentation period.

Astaxanthin production using fed-batch fermentation process by Phaffia rhodozyma

The present invention relates to a DNA encoding a novel flavin adenine dinucleotide (FAD)-dependent D-erythronate 4-phosphate (EN4P) dehydrogenase originated from, which is involved in vitamin B6 biosynthesis, and a recombinant microorganism transformed with a vector having the DNA. It also relates to a process for production of vitamin B6 by using the recombinant microorganism. 'Vitamin B6' as used in this invention includes pyridoxol (PN), pyridoxal and pyridoxamine. Vitamin B6 is a vitamin indispensable to human beings or other animals, and is used as a raw material of medicines or as feed additives.

Disclosed is a mutant of a recombinant microorganism of the genuscapable of producing vitamin Bhaving a recombinant plasmid with pdxJ gene that acquired histidine requirement of glycine resistance, or its combination thereof.

Process for producing vitamin B6

The present invention relates to a gene useful in a process to increase the microbial production of carotenoids. The carotenoids astaxanthin is distributed in a wide variety of organisms such as animals, algae and microorganisms. It has a strong antioxidation property against reactive oxygen species. Astaxanthin is used as a coloring reagent, especially in the industry of farmed fish, such as salmon, because astaxanthin imparts distinctive orange-red coloration to the animals and contributes to consumer appeal in the marketplace.

SQS gene

The present invention provides a process for the production of vitamin C from different substrates like D-sorbitol, L-sorbose, L-sorbosone or L-gulose using a microorganism selected from the group consisting ofDMS 4025 (FERM BP-3812), a microorganism belonging to the genusand having identifying characteristics ofDSM 4025 (FERM BP-3812) and mutants thereof.

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Kamakura, Japan

Tatsuo Hoshino