Tetracenomycin M, a novel genetically engineered tetracenomycin resulting from a combination of mithramycin and tetracenomycin biosynthetic genes

Chemistry - A European Journal

Volumn 3, Issue 10, 1997, Pages 1675-1678

  Künzel, Eva ^a   Wohlert, Sven Eric ^a   Beninga, Claus ^a   Haag, Sabine ^d   Decker, Heinrich ^d   Hutchinson, C Richard ^b   Blanco, Gloria ^c   Mendez, Carmen ^c   Salas, Jose A ^c   Rohr, Jürgen ^a  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

^b UNIVERSITY OF WISCONSIN MADISON   (United States)

^c UNIVERSITY OF OVIEDO   (Spain)

^d NONE

Author keywords

Antibiotics; Biosynthesis; Gene technology; Polyketides; Tetracenomycins

Indexed keywords

EID: 0039708954     PISSN: 09476539     EISSN: None     Source Type: Journal    
DOI: 10.1002/chem.19970031017     Document Type: Article

References (47)

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32. A function of the MtmX protein could not be assigned after comparison with proteins in data bases (GenBank, EMBL; Swissprotein). It has much similarity with gene products involved in other polyketide biosyntheses: the ActVI-orfA of the actinorhodin biosynthetic pathway (33.3% identical amino acids), and the product of an open reading frame (orfX) from the frenolicin biosynthetic pathway (37.6% identical amino acids); see: a) M. A. Fernández-Moreno, E. Martínez, J. L. Caballeros, K. Ichinose, D. A. Hopwood, F. Malpartida, J. Biol. Chem. 1994, 269, 24854-24863; b) M. J. Bibb, D. H. Sherman, S. Omura, D. A. Hopwood, Gene 1994, 142, 31-39. However, the dpsH gene ( C. Scotti and C. R. Hutchinson, J. Bacteriol. 1996, 178, 73 216-73 219), another mtmX homologue, has recently been shown to be a polyketide cyclase for daunorubicin biosynthesis (M. Gerlitz, K. Madduri, G. Meurer, E. Wendt-Pienkowski, C. R. Hutchinson, J. Am. Chem. Soc. 1997, 119, in press).
33. A function of the MtmX protein could not be assigned after comparison with proteins in data bases (GenBank, EMBL; Swissprotein). It has much similarity with gene products involved in other polyketide biosyntheses: the ActVI-orfA of the actinorhodin biosynthetic pathway (33.3% identical amino acids), and the product of an open reading frame (orfX) from the frenolicin biosynthetic pathway (37.6% identical amino acids); see: a) M. A. Fernández-Moreno, E. Martínez, J. L. Caballeros, K. Ichinose, D. A. Hopwood, F. Malpartida, J. Biol. Chem. 1994, 269, 24854-24863; b) M. J. Bibb, D. H. Sherman, S. Omura, D. A. Hopwood, Gene 1994, 142, 31-39. However, the dpsH gene ( C. Scotti and C. R. Hutchinson, J. Bacteriol. 1996, 178, 73 216-73 219), another mtmX homologue, has recently been shown to be a polyketide cyclase for daunorubicin biosynthesis (M. Gerlitz, K. Madduri, G. Meurer, E. Wendt-Pienkowski, C. R. Hutchinson, J. Am. Chem. Soc. 1997, 119, in press).
34. A function of the MtmX protein could not be assigned after comparison with proteins in data bases (GenBank, EMBL; Swissprotein). It has much similarity with gene products involved in other polyketide biosyntheses: the ActVI-orfA of the actinorhodin biosynthetic pathway (33.3% identical amino acids), and the product of an open reading frame (orfX) from the frenolicin biosynthetic pathway (37.6% identical amino acids); see: a) M. A. Fernández-Moreno, E. Martínez, J. L. Caballeros, K. Ichinose, D. A. Hopwood, F. Malpartida, J. Biol. Chem. 1994, 269, 24854-24863; b) M. J. Bibb, D. H. Sherman, S. Omura, D. A. Hopwood, Gene 1994, 142, 31-39. However, the dpsH gene ( C. Scotti and C. R. Hutchinson, J. Bacteriol. 1996, 178, 73 216-73 219), another mtmX homologue, has recently been shown to be a polyketide cyclase for daunorubicin biosynthesis (M. Gerlitz, K. Madduri, G. Meurer, E. Wendt-Pienkowski, C. R. Hutchinson, J. Am. Chem. Soc. 1997, 119, in press).
35. A function of the MtmX protein could not be assigned after comparison with proteins in data bases (GenBank, EMBL; Swissprotein). It has much similarity with gene products involved in other polyketide biosyntheses: the ActVI-orfA of the actinorhodin biosynthetic pathway (33.3% identical amino acids), and the product of an open reading frame (orfX) from the frenolicin biosynthetic pathway (37.6% identical amino acids); see: a) M. A. Fernández-Moreno, E. Martínez, J. L. Caballeros, K. Ichinose, D. A. Hopwood, F. Malpartida, J. Biol. Chem. 1994, 269, 24854-24863; b) M. J. Bibb, D. H. Sherman, S. Omura, D. A. Hopwood, Gene 1994, 142, 31-39. However, the dpsH gene ( C. Scotti and C. R. Hutchinson, J. Bacteriol. 1996, 178, 73 216-73 219), another mtmX homologue, has recently been shown to be a polyketide cyclase for daunorubicin biosynthesis (M. Gerlitz, K. Madduri, G. Meurer, E. Wendt-Pienkowski, C. R. Hutchinson, J. Am. Chem. Soc. 1997, 119, in press).
36. a) A decarboxylation occurs in the tetracenomycin biosynthetic pathway in connection with the formation of the shunt product tetracenomycin D, but it is also required for mithramycin biosynthesis. Since there is no decarboxylase gene in the mtm XhoI fragment, it is more likely that this step is catalyzed by the original host-strain genes or that it occurs spontaneously. See also: a) S. Yue, H. Motamedi, E. Wendt-Pienkowski, C. R. Hutchinson, J. Bacteriol. 1986, 167, 581-586; b) J. Rohr, S. Eick, A. Zeeck, P. Reuschenbach, H. Zähner, H.-P. Fiedler, J. Antibiot. 1988, 41, 1066-1073; b) The gene cluster of tetracenomycin C biosynthesis does not contain any ketoreductase-coding gene fragment, and such activity is not necessary for formation of tetracenomycin C, but a ketoreductase activity may be encoded elsewhere in the genome of S. glaucescens.
37. a) A decarboxylation occurs in the tetracenomycin biosynthetic pathway in connection with the formation of the shunt product tetracenomycin D, but it is also required for mithramycin biosynthesis. Since there is no decarboxylase gene in the mtm XhoI fragment, it is more likely that this step is catalyzed by the original host-strain genes or that it occurs spontaneously. See also: a) S. Yue, H. Motamedi, E. Wendt-Pienkowski, C. R. Hutchinson, J. Bacteriol. 1986, 167, 581-586; b) J. Rohr, S. Eick, A. Zeeck, P. Reuschenbach, H. Zähner, H.-P. Fiedler, J. Antibiot. 1988, 41, 1066-1073; b) The gene cluster of tetracenomycin C biosynthesis does not contain any ketoreductase-coding gene fragment, and such activity is not necessary for formation of tetracenomycin C, but a ketoreductase activity may be encoded elsewhere in the genome of S. glaucescens.
38. a) A decarboxylation occurs in the tetracenomycin biosynthetic pathway in connection with the formation of the shunt product tetracenomycin D, but it is also required for mithramycin biosynthesis. Since there is no decarboxylase gene in the mtm XhoI fragment, it is more likely that this step is catalyzed by the original host-strain genes or that it occurs spontaneously. See also: a) S. Yue, H. Motamedi, E. Wendt-Pienkowski, C. R. Hutchinson, J. Bacteriol. 1986, 167, 581-586; b) J. Rohr, S. Eick, A. Zeeck, P. Reuschenbach, H. Zähner, H.-P. Fiedler, J. Antibiot. 1988, 41, 1066-1073; b) The gene cluster of tetracenomycin C biosynthesis does not contain any ketoreductase-coding gene fragment, and such activity is not necessary for formation of tetracenomycin C, but a ketoreductase activity may be encoded elsewhere in the genome of S. glaucescens.
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