Methods and microorganisms for production of panto-compounds

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/52 (2006.01) C12N 9/00 (2006.01) C12N 9/02 (2006.01) C12N 9/10 (2006.01) C12N 9/12 (2006.01) C12N 9/88 (2006.01) C12N 15/53 (2006.01) C12N 15/54 (2006.01) C12N 15/60 (2006.01) C12N 15/75 (2006.01) C12P 7/42 (2006.01) C12P 13/02 (2006.01) C12P 13/06 (2006.01) C12P 17/04 (2006.01)

Patent

CA 2385497

The present invention features methods of producing panto-compounds (<i>e.g.</i>, pantothenate) using microorganisms in which the pantothenate biosynthetic pathway and/or the isoleucine-valine biosynthetic pathway and/or the coenzymeA biosynthetic pathway has been manipulated. Methods featuring ketopantoate reductase overexpressing microorganisms as well as aspartate g(a)- decarboxylase overexpressing microorganisms are provided. Methods of producing panto-compounds in a precursor-independent manner and in high yield are described. Recombinant microorganisms, vectors, isolated nucleic acid molecules, genes and gene products useful in practicing the above methodologies are also provided. The present invention also features a previously microbial pantothenate kinase gene, <i>coaX</i>, as well as methods of producing panto-compounds utilizing microorganisms having modified pantothenate kinase activity. Recombinant microorganisms, vectors, isolated <i>coaX</i> nucleic acid molecules and purified CoaX proteins are featured. Also featured are methods for identifying pantothenate kinase modulators utilizing the recombinant microorganisms and/or purified CoaX proteins of the present invention.

L'invention concerne des procédés de production de composés panto (par exemple pantothénate) à l'aide de micro-organismes dans lesquels on a manipulé la voie de synthèse biologique du pantothénate et/ou la voie de synthèse biologique d'isoleucine-valine et/ou la voie de synthèse biologique de la coenzyme A. Des procédés concernant des micro-organismes surexprimant kétopantoate réductase et des micro-organismes surexprimant l'aspartate .alpha.-décarboxylase sont également traités, ainsi que des procédés de fabrication de composés panto sans précurseur et à haut rendement. Des micro-organismes de recombinaison, des vecteurs, des molécules d'acide nucléique, des gènes et des produits géniques utiles à l'exercice des méthodologies précitées sont également traités. L'invention porte en outre sur un gène de kinase pantothénate microbien antérieurement non identifié, <i>coaX</i>, et sur des procédés de production de composés panto faisant appel à des micro-organismes présentant une activité de kinase pantothénate modifiée, ainsi que sur des micro-organismes de recombinaison, des vecteurs, des molécules d'acide nucléique <i>coaX</i> isolées et des protéines <i>coaX</i> purifiées. L'invention traite enfin de procédés permettant d'identifier des modulateurs de kinase pantothénate utilisant les micro-organismes de recombinaison et/ou des protéines <i>coaX </i> purifiées.

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