Methods for producing hyaluronic acid in a bacillus cell

C - Chemistry – Metallurgy – 12 – P

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C12P 19/26 (2006.01) C12N 1/21 (2006.01) C12N 15/11 (2006.01) C12N 15/63 (2006.01) C12N 15/75 (2006.01) C12P 19/04 (2006.01)

Patent

CA 2563173

The present invention relates to methods for producing a hyaluronic acid, comprising: (a) cultivating a Bacillus host cell in a medium conducive for the production of the hyaluronic acid, wherein the Bacillus cell comprises a nucleic acid construct comprising a triple promoter comprising a variant amylpromoter having a mutation corresponding to position 590 of SEQ ID NO: 1, a consensus promoter having the sequence TTGACA for the "-35" region and TATART for the "-10" region, and a cryIIIA promoter, in which each promoter sequence of the triple promoter is operably linked to one or more coding sequences involved in the biosynthesis of the hyaluronic acid; and (b) isolating the hyaluronic acid from the cultivation medium. The present invention also relates to Bacillus cells comprising a nucleic acid construct which comprises (i) a triple promoter comprising a variant amyl promoter having a mutation corresponding to position 590 of SEQ ID NO: 1, a consensus promoter having the sequence TTGACA for the "-35" region and TATART for the "- 10" region, and a cryIIIA promoter, in which each promoter sequence of the triple promoter is operably linked to one or more coding sequences involved in the biosynthesis of the hyaluronic acid.

Méthodes de production d'acide hyaluronique qui consistent (a) à cultiver une cellule hôte de Bacillus dans un milieu favorable à la production d'acide hyaluronique, ladite cellule de Bacillus comportant un produit de recombinaison d'acide nucléique comprenant un triple promoteur constitué d'un promoteur amyL variant présentant une mutation correspondant à la position 590 de SEQ ID NO: 1, d'un promoteur à séquences consensus comportant la séquence TTGACA pour la région "-35" et TATAAT pour la région "-10" et d'un promoteur crylllA, chaque séquence de promoteur du triple promoteur étant fonctionnellement liée à une ou plusieurs séquences codantes impliquées dans la biosynthèse de l'acide hyaluronique et (b) à isoler l'acide hyaluronique du milieu de culture. La présente invention concerne également des cellules de Bacillus contenant un produit de recombinaison d'acide nucléique qui comporte (i) un triple promoteur constitué d'un promoteur amyL variant présentant une mutation correspondant à la position 590 de SEQ ID NO: 1, un promoteur à séquences consensus comportant la séquence TTGACA pour la région "-35" et TATAAT pour la région "-10" et un promoteur crylllA, chaque séquence de promoteur du triple promoteur étant fonctionnellement liée à une ou plusieurs séquences codantes impliquées dans la biosynthèse de l'acide hyaluronique.

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