Biosynthesis of Aromatic Polyketides

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Aromatic polyketides differ from other polyketides by their characteristic polycyclic aromatic structures. These polyketides are widely distributed in bacteria, fungi, and plants, and many of them are clinically valuable agents or exhibit other fascinating biological activities. Analogous to fatty acids and reduced polyketide biosynthesis, aromatic polyketide biosynthesis is accomplished by the polyketide synthases that catalyze sequential decarboxylative condensation between the starter and extender units to yield a linear poly-β-ketone intermediate. The latter undergoes regiospecific reduction, aromatization, or cyclization to furnish the polycyclic aromatic structures, which are further modified by tailoring enzymes to imbue them with various biological activities. This review begins with a brief discussion on the architectural organizations among various polyketide synthase genes and genetic contributions to understanding polyketide synthases. It then presents a comprehensive account of the most recent advances in the biochemistry and enzymology of bacterial, fungal, and plant polyketide synthases, with emphasis on in vitro studies. It concludes with a cautious summary of the so-called design-rules to guide rational engineering of polyketide synthases for the synthesis of novel aromatic polyketides.