TY - JOUR
T1 - Cloning and characterization of a Myxococcus xanthus cytochrome P-450 hydroxylase required for biosynthesis of the polyketide antibiotic TA
AU - Paitan, Yossi
AU - Orr, Elisha
AU - Ron, Eliora Z.
AU - Rosenberg, Eugene
N1 - Funding Information:
This work was supported in part by the Pasha Gol Chair for Applied Microbiology (E.R.), the Morris and Manja Leigh Chair for Biophsics and Biotechnology (E.Z.R.), a FEMS Research fellowship awarded to Y.P., and Cancer Research Campaign (No. SP1937/0301) and Wellcome Trust (No. 038060/Z/93/Z) grants to E.O.
PY - 1999/3/4
Y1 - 1999/3/4
N2 - The antibiotic TA, a complex macrocyclic polyketide of Myxococcus xanthus, is produced, like many other polyketides, through successive condensations of acetate by a type I polyketide synthase (PKS) mechanism. The chemical structure of this antibiotic and the mechanism by which it is synthesized indicate the need for several post-modification steps, such as a specific hydroxylation at C-20. Previous studies have shown that several genes, essential for TA biosynthesis, are clustered in a region of at least 36 kb, which was subsequently cloned and analyzed. In this study, we report the analysis of a DNA fragment, containing a specific cytochrome P-450 hydroxylase, presumably responsible for the sole non-PKS hydroxylation at position C-20. Functional analysis of the cytochrome P-450 hydroxylase gene through specific gene disruption confirms that it is essential for the production of an active TA molecule.
AB - The antibiotic TA, a complex macrocyclic polyketide of Myxococcus xanthus, is produced, like many other polyketides, through successive condensations of acetate by a type I polyketide synthase (PKS) mechanism. The chemical structure of this antibiotic and the mechanism by which it is synthesized indicate the need for several post-modification steps, such as a specific hydroxylation at C-20. Previous studies have shown that several genes, essential for TA biosynthesis, are clustered in a region of at least 36 kb, which was subsequently cloned and analyzed. In this study, we report the analysis of a DNA fragment, containing a specific cytochrome P-450 hydroxylase, presumably responsible for the sole non-PKS hydroxylation at position C-20. Functional analysis of the cytochrome P-450 hydroxylase gene through specific gene disruption confirms that it is essential for the production of an active TA molecule.
KW - Cytochrome P-450 hydroxylase
KW - Hydroxylation
KW - PKS
KW - Polyketides
UR - http://www.scopus.com/inward/record.url?scp=0033522168&partnerID=8YFLogxK
U2 - 10.1016/S0378-1119(98)00609-X
DO - 10.1016/S0378-1119(98)00609-X
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AN - SCOPUS:0033522168
SN - 0378-1119
VL - 228
SP - 147
EP - 153
JO - Gene
JF - Gene
IS - 1-2
ER -