5BP1

Condensing di-domain (KS-AT) of a mycocerosic acid synthase-like (MAS-like) PKS

Summary for 5BP1

• Entry DOI: 10.2210/pdb5bp1/pdb
• Related: 5BP2 5BP3 5BP4
• Descriptor: Mycocerosic acid synthase (2 entities in total)
• Functional Keywords: polyketide, ketosynthase, acyltransferase, transferase
• Biological source: Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
• Cellular location: Cell membrane ; Lipid-anchor : A0R1E8
• Total number of polymer chains: 1
• Total formula weight: 93684.20

Authors

Jakob, R.P.,Herbst, D.A.,Zaehringer, F.,Maier, T. (deposition date: 2015-05-27, release date: 2016-03-09, Last modification date: 2024-01-10)

Primary citation

Herbst, D.A.,Jakob, R.P.,Zahringer, F.,Maier, T.
Mycocerosic acid synthase exemplifies the architecture of reducing polyketide synthases.
Nature, 531:533-537, 2016

PubMed Abstract: Polyketide 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.

PubMed: 26976449
DOI: 10.1038/nature16993

Experimental method

X-RAY DIFFRACTION (2.203 Å)