5BP2

Dehydratase domain (DH) of a mycocerosic acid synthase-like (MAS-like) PKS, crystal form 1

Summary for 5BP2

• Entry DOI: 10.2210/pdb5bp2/pdb
• Related: 5BP3 5BP4 5BP5
• Descriptor: Mycocerosic acid synthase-like polyketide synthase, MAGNESIUM ION, 1,2-ETHANEDIOL, ... (7 entities in total)
• Functional Keywords: lyase, pks, dehydratase, dh, polyketide
• Biological source: Mycobacterium smegmatis
• Cellular location: Cell membrane ; Lipid-anchor : A0R1E8
• Total number of polymer chains: 4
• Total formula weight: 131143.67

Authors

Herbst, D.A.,Jakob, P.R.,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 (1.75 Å)