RESUMEN
Polyketides are a large family of structurally complex natural products including compounds with important bioactivities. Polyketides are biosynthesized by polyketide synthases (PKSs), multienzyme complexes derived evolutionarily from fatty acid synthases (FASs). The focus of this review is to critically compare the properties of FASs with iterative aromatic PKSs, including type II PKSs and fungal type I nonreducing PKSs whose chemical logic is distinct from that of modular PKSs. This review focuses on structural and enzymological studies that reveal both similarities and striking differences between FASs and aromatic PKSs. The potential application of FAS and aromatic PKS structures for bioengineering future drugs and biofuels is highlighted.
Asunto(s)
Ácido Graso Sintasas/química , Ácido Graso Sintasas/metabolismo , Sintasas Poliquetidas/química , Sintasas Poliquetidas/metabolismo , Animales , Biocatálisis , Productos Biológicos/química , Productos Biológicos/metabolismo , Ácido Graso Sintasas/clasificación , Humanos , Modelos Moleculares , Imitación Molecular , Estructura Molecular , Sintasas Poliquetidas/clasificación , Policétidos/química , Policétidos/metabolismo , Dominios Proteicos , Homología Estructural de Proteína , Especificidad por SustratoRESUMEN
This chapter describes structural and associated enzymological studies of polyketide synthases, including isolated single domains and multidomain fragments. The sequence-structure-function relationship of polyketide biosynthesis, compared with homologous fatty acid synthesis, is discussed in detail. Structural enzymology sheds light on sequence and structural motifs that are important for the precise timing, substrate recognition, enzyme catalysis, and protein-protein interactions leading to the extraordinary structural diversity of naturally occurring polyketides.