Polyketide synthases type III

Austin MB and Noel IP. 2003. The chalcone synthase superfamily of type III polyketide synthases. Nat Prod Rep 20 79-110. 

STRUCTURALLY GUIDED ALTERATION OF BIOSYNTHESIS IN PLANT TYPE III POLYKETIDE SYNTHASES... 

In this chapter, we describe the atomic resolution structural elucidation of several plant type III polyketide synthases, including chalcone synthase, 2-pyrone synthase, and stilbene synthase. Manipulation of the catalytic activity and specificity of these biosynthetic enzymes by using a structurally guided approach offers a novel... 

SeshimeY etai, Discovery of a novel superfamily of type III polyketide synthases m Aspergillus oryzae, Biochem Biophys Res Commun 331 253-260, 2005. 

Noel, J.P. et al., Structurally guided alteration of biosynthesis in plant type III polyketide synthases, in Phytochemistry in the Genomics and Post-Genomics Eras, Romeo, J.T. and Dixon, R.A., Eds., Pergamon, New York, 2002, 197. 

Keywords Chalcone synthase superfamily enzyme, Engineered biosynthesis, Precursor-directed biosynthesis, Structure-based engineering, Type III polyketide synthase... 

The chalcone synthase (CHS) (EC 2.3.1.74) superfamily of type III Polyketide synthases (PKSs) are pivotal enzymes in the biosynthesis of plant polyphenols. They are structurally and mechanistically different from the modular type I and the dissociated type II PKSs of bacterial origin the simple homodimer of 4CM-5 kDa proteins performs a complete series of decarboxylation, condensation, cyclization,... 

Austin MB, Bowman ME, Ferrer J-L, Schroder J, Noel JP (2004) An aldol switch discovered in stilbene synthases mediates cyclization specificity of Type III polyketide synthases. Chem Biol 11 1179-1194... 

Wanibuchi K, Zhang P, Abe T, Morita H, Kohno T, Qien G, Noguchi H (2007) An acridone-producing novel multifunctional type III polyketide synthase from Huperzia serrata. FEBS J 274 1073-1082... 

Abe I, Sano Y, Takahashi Y, Noguchi H (2003) Site-directed mutagenesis of benzalacetone synthase the role of Phe215 in plant type III polyketide synthases. J Biol Chem 278 25218-25226... 

Morita H, Tanio M, Kondo S, Kato R, Wanibuchi K, Noguchi H, Sugio S, Abe I, Kohno T (2008) Crystallization and preliminary crystallographic analysis of a plant type III polyketide synthase that produces benzalacetone. Acta Crystallograph Sect F Struct Biol Cryst Commun 64 304-306... 

Abe I, Utsumi Y, Oguro S, Noguchi H (2004) The Hrst plant type III polyketide synthase catalyzing formation of aromatic heptaketide. FEBS Lett 562 171-176... 

Katsuyama Y, Matsuzawa M, Funa N, Horinouchi S (2007) In vitro synthesis of curcuminoids by type III polyketide synthase from Oryza sativa. J Biol Chem 282 37702-37709... 

Katsuyama Y, Kita T, Funa N, Horinouchi S (2009) Curcuminoid biosynthesis by two type III polyketide synthases in the herb Curcuma longa. J Biol Chem 284 11160-11170... 

Austin MB, Izumikawa M, Bowman ME, Udwary DW, Ferrer JL, Moore BS, Noel JP (2004) Crystal structure of a bacterial type III polyketide synthase and enzymatic control of reactive polyketide intermediates. J Biol Chem 279 45162-45174... 

Abe I, Oguro S, Utsumi Y, Sano Y, Noguchi H (2005) Engineered biosynthesis of plant polyketides chain length control in an octaketide-producing plant Type III polyketide synthase. J Am Chem Soc 127 12709-12716... 

Mizuuchi Y, Shi S-P, Wanibuchi K, Kojima A, Morita H, Noguchi H, Abe I (2009) Novel type III polyketide synthases from Aloe arborescens. FEBS J 276 2391-2401... 

Karppinen K, Hokkanen J, Manila S, Neubauer P, Hohtola A (2008) Octaketide-producing type III polyketide synthase from Hypericum perforatum is expressed in dark glands accumulating hypericins. FEBS J 275 4329-4342... 

Jindaprasert A, Springob K, Schmidt J, De-Eknamkul W, Kutchan TM (2008) Pyrone polyketides synthesized by a type III polyketide synthase from Drosophyllum lusitanicum. Phytochemistry 69 3043-3053... 

Abe I, Watanabe T, Noguchi H (2004) Enzymatic formation of long-chain polyketide pyrones by plant type III polyketide synthases. Phytochemistry 65 2447-2453... 

Jez JM, Bowman ME, Noel JP (2002) Expanding the biosynthetic repertoire of plant type III polyketide synthases by altering starter molecule specificity. Proc Natl Acad Sci USA 99 5319-5324... 

Type III polyketide synthases represent an evolutionarily distinct sub-type, and are less structurally and catalytically complex than the type I and II enzymes. In general, the type III enzymes have no significant similarity at the primaiy sequence level to either FAS or other PKS sub-types, and likely arose via an entirely distinct evolutionary path 24). Initially, type III PKSs were designated as plant-specific , however in more recent years type III synthases have also been characterized from bacteria e.g., 28). Additionally, the presence of related sequences identified within the sequenced genomes of numerous bacterial species strongly suggests that the blueprint for type III enzymes pre-dates their adaptation for use by land plants 24,25). 

Type III polyketide synthases are responsible for the biosynthesis of a vast number of plant-derived natural products, including flavonoids derived from the important branch metabolite 4 ,2 ,4 ,6 -tetrahydroxychalcone, the product of the enzyme chalcone synthase (39). Because chalcone synthase was the first type III enzyme discovered, and a second flavonoid pathway type III enzyme, stilbene synthase, was discovered shortly thereafter, type III PKSs are also collectively referred to as the chalcone synthase/stilbene synthase superfamily of enzymes (24,25). 

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