5bp4
Modifying region (DH-ER-KR) of a mycocerosic acid synthase-like (MAS-like) PKSModifying region (DH-ER-KR) of a mycocerosic acid synthase-like (MAS-like) PKS
Structural highlights
Warning: this is a large structure, and loading might take a long time or not happen at all. Publication Abstract from PubMedPolyketide synthases (PKSs) are biosynthetic factories that produce natural products with important biological and pharmacological activities. Their exceptional product diversity is encoded in a modular architecture. Modular PKSs (modPKSs) catalyse reactions colinear to the order of modules in an assembly line, whereas iterative PKSs (iPKSs) use a single module iteratively as exemplified by fungal iPKSs (fiPKSs). However, in some cases non-colinear iterative action is also observed for modPKSs modules and is controlled by the assembly line environment. PKSs feature a structural and functional separation into a condensing and a modifying region as observed for fatty acid synthases. Despite the outstanding relevance of PKSs, the detailed organization of PKSs with complete fully reducing modifying regions remains elusive. Here we report a hybrid crystal structure of Mycobacterium smegmatis mycocerosic acid synthase based on structures of its condensing and modifying regions. Mycocerosic acid synthase is a fully reducing iPKS, closely related to modPKSs, and the prototype of mycobacterial mycocerosic acid synthase-like PKSs. It is involved in the biosynthesis of C20-C28 branched-chain fatty acids, which are important virulence factors of mycobacteria. Our structural data reveal a dimeric linker-based organization of the modifying region and visualize dynamics and conformational coupling in PKSs. On the basis of comparative small-angle X-ray scattering, the observed modifying region architecture may be common also in modPKSs. The linker-based organization provides a rationale for the characteristic variability of PKS modules as a main contributor to product diversity. The comprehensive architectural model enables functional dissection and re-engineering of PKSs. Mycocerosic acid synthase exemplifies the architecture of reducing polyketide synthases.,Herbst DA, Jakob RP, Zahringer F, Maier T Nature. 2016 Mar 24;531(7595):533-7. doi: 10.1038/nature16993. Epub 2016 Mar 14. PMID:26976449[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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