Austin Michael B, Noel Joseph P
Structural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Nat Prod Rep. 2003 Feb;20(1):79-110. doi: 10.1039/b100917f.
This review covers the functionally diverse type III polyketide synthase (PKS) superfamily of plant and bacterial biosynthetic enzymes. from the discovery of chalcone synthase (CHS) in the 1970s through the end of 2001. A broader perspective is achieved by a comparison of these CHS-like enzymes to mechanistically and evolutionarily related families of enzymes, including the type I and type II PKSs, as well as the thiolases and beta-ketoacyl synthases of fatty acid metabolism. As CHS is both the most frequently occurring and best studied type III PKS, this enzyme's structure and mechanism is examined in detail. The in vivo functions and biological activities of several classes of plant natural products derived from chalcones are also discussed. Evolutionary mechanisms of type III PKS divergence are considered, as are the biological functions and activities of each of the known and functionally divergent type III PKS enzymc families (currently twelve in plants and three in bacteria). A major focus of this review is the integration of information from genetic and biochemical studies with the unique insights gained from protein X-ray crystallography and homology modeling. This structural approach has generated a number of new predictions regarding both the importance and mechanistic role of various amino acid substitutions observed among functionally diverse type III PKS enzymes.
本综述涵盖了植物和细菌生物合成酶中功能多样的III型聚酮合酶（PKS）超家族。从20世纪70年代查尔酮合酶（CHS）的发现到2001年底。通过将这些类CHS酶与机制和进化相关的酶家族进行比较，可获得更广阔的视角，这些酶家族包括I型和II型PKS，以及脂肪酸代谢中的硫解酶和β-酮酰基合成酶。由于CHS是最常见且研究最深入的III型PKS，因此对该酶的结构和机制进行了详细研究。还讨论了几类源自查尔酮的植物天然产物的体内功能和生物活性。考虑了III型PKS分化的进化机制，以及每个已知的且功能多样的III型PKS酶家族（目前植物中有12个，细菌中有3个）的生物学功能和活性。本综述的一个主要重点是将遗传和生化研究的信息与蛋白质X射线晶体学和同源建模获得的独特见解相结合。这种结构方法对功能多样的III型PKS酶中观察到的各种氨基酸取代的重要性和机制作用产生了许多新的预测。
