Dsm IP Assets B.v.

Dsm N.v.

Dick Schipper

Masako Shinjoh

Bertus Pieter Koekman

Nigel John Mouncey

Connie Lee

Anja Meury

Adrianus W H Vollebregt

Anne F Mayer

Corina Hauk

Markus G Goese

Christine Toepfer

Marina Van Gelder

Manuela Dalluege

Emilius Johannes Albertus Xaverius Van De Sandt

Marie-Gabrielle Beuzelin-Ollivier

Bastien Chevreux

Martina Beishuizen

Robertus Antonius Mijndert Van Der Hoeven

Noel Nicolaas Maria Elisabeth Van Peij

Marcus Hans

Olaf Leonardus Schouten

Bastian Chevreux

Ilco Adrainus Lambertus Antonius Boogers

Ilco Adrianus Lambertus Antonius Boogers

Van Noël Nicolaas Maria Elisabeth Peij

Van Der Robertus Antonius Mijndert Hoeven

The present invention relates to newly identified microorganisms capable of direct production of L-ascorbic acid (hereinafter also referred to as Vitamin C). The invention also relates to polynucleotide sequences comprising genes that encode proteins which are involved in the synthesis of 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 said polynucleotides and polypeptides as biotechnological tools in the production of Vitamin C from microorganisms, whereby a modification of said polynucleotides and/or encoded polypeptides has a direct or indirect impact on yield, production, and/or efficiency of production of the fermentation product in said 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.

Fermentative Vitamin C production

The present invention relates to a method for the production of a compound of interest by microbial fermentation, wherein the microbial host cell used has been modified in its genome such that it results in a deficiency in the production of at least one non-ribosomal peptide synthase. The present invention further relates to a microbial host cell that has been modified in its genome such that it results in a deficiency in the production of at least one non-ribosomal peptide synthase. The invention further relates to a compound of interest.

Recombinant host cell with deficiency in non-ribosomal peptide synthase production

Fermentative vitamin C production

A method for the recovery of an N-substituted cephalosporanic acid compound of general formula (I), wherein R is selected from the group consisting of adipyl (1,4-dicarboxybutane), succinyl, glutaryl, adipyl, pimelyl, suberyl, 2-carboxyethyithio)acetyl, 3-carboxyethylthio)propionyl, higher alkyl saturated and higher alkyl unsaturated dicarboxylic acids, from a complex mixture comprising in addition to the compound of general formula (I) 6-aminopenicillanic acid (6-APA) and optionally one or more N-substituted penicillanic acid compounds, comprising the steps of: (a) acidifying the complex mixture to a pH below 6.5 and maintaining the mixture below said pH at a temperature of between 10&deg; C. and 150&deg; C.; and/or (b) contacting the complex mixture with a carbon dioxide source; and (c) recovering the cephalosporanic acid compound of formula (I) from the mixture obtained after steps (a) and/or (b).

Process for the fermentative production of cephalosporin

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Delft, Netherlands

Dick Schipper