title: Identification and characterization of a type III polyketide synthase involved in quinolone alkaloid biosynthesis from Aegle marmelos Correa.
abstract: Quinolone alkaloids, found abundantly in the roots of bael (Aegle marmelos), possess various biological activities and have recently gained attention as potential lead molecules for novel drug designing. Here, we report the characterization of a novel Type III polyketide synthase, quinolone synthase (QNS), from A. marmelos that is involved in the biosynthesis of quinolone alkaloid. Using homology-based structural modeling, we identify two crucial amino acid residues (Ser-132 and Ala-133) at the putative QNS active site. Substitution of Ser-132 to Thr and Ala-133 to Ser apparently constricted the active site cavity resulting in production of naringenin chalcone from p-coumaroyl-CoA. Measurement of steady-state kinetic parameters demonstrates that the catalytic efficiency of QNS was severalfold higher for larger acyl-coenzymeA substrates as compared with smaller precursors. Our mutagenic studies suggest that this protein might have evolved from an evolutionarily related member of chalcone synthase superfamily by mere substitution of two active site residues. The identification and characterization of QNS offers a promising target for gene manipulation studies toward the production of novel alkaloid scaffolds.
authors: Plant Molecular Biology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud (P.O), Thiruvananthapuram, 695 014 Kerala, India.
authors: Mohankumar Saraladevi
authors: MS
authors: Resmi
authors: Priyanka
authors: P
authors: Verma
authors: Rajesh S
authors: RS
authors: Gokhale
authors: Eppurathu Vasudevan
authors: EV
authors: Soniya
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D045471:Aegle / Q000235:genetics / Q000378:metabolism*; D000470:Alkaloids / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D055162:Biocatalysis; D020134:Catalytic Domain / Q000235:genetics; D047188:Chalcones / Q000378:metabolism; D003001:Cloning, Molecular; D007700:Kinetics; D013058:Mass Spectrometry / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048630:Polyketide Synthases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015363:Quinolones / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D000214:Acyl Coenzyme A; D000470:Alkaloids; D047188:Chalcones; D010940:Plant Proteins; D015363:Quinolones; C058644:4-coumaroyl-coenzyme A; C027329:naringenin chalcone; D048630:Polyketide Synthases