Eisai R&d Management Co., Ltd.

Micro Biopharm Japan Co., Ltd.

Mercian Corporation

Kazuhiro Machida

Atsushi Ochiai

Masashi Ito

Toshio Tsuchida

Tadashi Fujii

Yoshikazu Fujii

Takashi Nakashima

Masashi Itoh

Masashi Yoshida

Susumu Takeda

Asako Toyoda

Yasuhide Aritoku

Hiroki Kabumoto

Kaoru Okayama

Disclosed is a means for improving the poor conversion efficiency in a conventional bioconversion system using a transformant which is given by introducing a gene originated from xerogenic organisms. A transformant is prepared by using a host which is defective in a gene encoding a multidrug efflux protein and introducing a gene originated from xerogenic organisms. Use of the transformant results in much effective microbial conversion of a hydrophobic or amphipathic substrate compound into a desired compound. In case, anis used as the host, the gene encoding a multidrug efflux protein to be defective may be tolC, acrA, acrB and the like.

Transformed strains originated from multidrug efflux protein defective strains and a method for microbial conversion using them

The nucleotide sequence of a DNA involved in the biosynthesis of herboxidiene was determined. Utilizing this DNA, herboxidiene and analogues thereof can be efficiently produced.

DNA encoding polypeptide involved in biosynthesis of herboxidiene

Disclosed is a means for improving the poor conversion efficiency in a bioconversion system using ancell having a bacterium-originated cytochrome P-450 gene integrated therein. A recombinantcell is produced by introducing aciB and aciC which encode a gene for the electron transport system originated from thesp. OC4 strain into ancell, and adding a polynucleotide encoding an N-terminal sequence composed of 48 amino acid residues of AciA and the like to the 5'-terminus of a bacterium-originated cytochrome P-450 gene, wherein AciA is an alkane-oxidative cytochrome P-450 originated from thesp. OC4 strain. Use of the recombinantcell results in much effective microbial conversion of a hydrophobic or amphipathic substrate compound into a desired compound.

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The present invention provides polypeptides that participate in the biosynthesis of the pladienolide macrolide compounds, DNA that encodes these polypeptides and variants of this DNA, transformants that maintain all or a portion of this DNA or variant thereof, and a method of producing the pladienolide macrolide compounds using these transformants. More particularly, it provides an isolated pure DNA that contains at least one region encoding a polypeptide that participates in pladienolide biosynthesis; polypeptide encoded by this DNA; a self-replicating or integrated-replicating recombinant plasmid carrying this DNA; a transformant maintaining this DNA; and a method of producing a pladienolide, characterized by culturing this transformant on culture medium and collecting pladienolide from this culture medium.

DNA coding for polypeptide participating in biosynthesis of pladienolide

The present invention provides a DNA participating in biological transformation of a macrolide compound 11107B. The present invention provides, particularly, a DNA participating in biological transformation of a macrolide compound 11107B represented by the formula (I) into a 16-position hydroxy macrolide compound 11107D represented by the formula (II), the DNA encoding a protein having 16-position hydroxylating enzymatic activity or ferredoxin, to a method of isolating the DNA, to a protein encoded by the DNA, a plasmid carrying the DNA, a transformant obtained by transforming using the plasmid and a method of producing a 16-position hydroxy compound by using the transformant. 

DNA participating in hydroxylation of macrolide compound

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Shizuoka, Japan

Kazuhiro Machida