A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Sequential action of two flavoenzymes, PgaE and PgaM, in angucycline biosynthesis: Chemoenzymatic synthesis of gaudimycin C
Tekijät: Kallio P, Liu ZL, Mantsala P, Niemi J, Metsa-Ketela M
Kustantaja: CELL PRESS
Julkaisuvuosi: 2008
Lehti:: Chemistry and Biology
Tietokannassa oleva lehden nimi: CHEMISTRY & BIOLOGY
Lehden akronyymi: CHEM BIOL
Vuosikerta: 15
Numero: 2
Aloitussivu: 157
Lopetussivu: 166
Sivujen määrä: 10
ISSN: 1074-5521
DOI: https://doi.org/10.1016/j.chembiol.2007.12.011
Tiivistelmä
Tailoring steps in aromatic polyketide antibiotic biosynthesis are an important source of structural diversity and, consequently, an intriguing focal point for enzymological studies. PgaE and PgaM from Streptomyces sp. PGA64 are representatives of flavoenzymes catalyzing early post-PKS reactions in angucycline biosynthesis. This in vitro study illustrates that the chemoenzymatic conversion of UWM6 into the metabolite, gaudimycin C, requires multiple closely coupled reactions to prevent intermediate degradation. The NMR structure of gaudimycin C confirms that the reaction cascade involves C12-and C12b-hydroxylation, C2,3-dehydration, and stereospecific ketoreduction at C6. Enzymatic O-18 incorporation studies verify that the oxygens at C12 and C12b derive from O-2 and H2O, respectively. The results indicate that PgaM deviates mechanistically from flavoprotein monooxygenases, and suggest an alternative catalytic mechanism involving a quinone methide intermediate.
Tailoring steps in aromatic polyketide antibiotic biosynthesis are an important source of structural diversity and, consequently, an intriguing focal point for enzymological studies. PgaE and PgaM from Streptomyces sp. PGA64 are representatives of flavoenzymes catalyzing early post-PKS reactions in angucycline biosynthesis. This in vitro study illustrates that the chemoenzymatic conversion of UWM6 into the metabolite, gaudimycin C, requires multiple closely coupled reactions to prevent intermediate degradation. The NMR structure of gaudimycin C confirms that the reaction cascade involves C12-and C12b-hydroxylation, C2,3-dehydration, and stereospecific ketoreduction at C6. Enzymatic O-18 incorporation studies verify that the oxygens at C12 and C12b derive from O-2 and H2O, respectively. The results indicate that PgaM deviates mechanistically from flavoprotein monooxygenases, and suggest an alternative catalytic mechanism involving a quinone methide intermediate.
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