5bp4
Modifying region (DH-ER-KR) of a mycocerosic acid synthase-like (MAS-like) PKS
Structural highlights
FunctionPKS5_MYCS2 Polyketide synthase involved in the biosynthesis of 2,4-dimethyl-2-eicosenoic acid, a lipid component of the lipooligosaccharides (LOS) which are not located at the bacterial surface but rather in deeper compartments of the cell envelope of M.smegmatis.[1] 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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