Structure and conformational variability of the mycobacterium tuberculosis fatty acid synthase multienzyme complex

Structure. 2013 Jul 2;21(7):1251-7. doi: 10.1016/j.str.2013.04.023. Epub 2013 Jun 6.


Antibiotic therapy in response to Mycobacterium tuberculosis infections targets de novo fatty acid biosynthesis, which is orchestrated by a 1.9 MDa type I fatty acid synthase (FAS). Here, we characterize M. tuberculosis FAS by single-particle cryo-electron microscopy and interpret the data by docking the molecular models of yeast and Mycobacterium smegmatis FAS. Our analysis reveals a porous barrel-like structure of considerable conformational variability that is illustrated by the identification of several conformational states with altered topology in the multienzymatic assembly. This demonstrates that the barrel-like structure of M. tuberculosis FAS is not just a static scaffold for the catalytic domains, but may play an active role in coordinating fatty acid synthesis. The conception of M. tuberculosis FAS as a highly dynamic assembly of domains revises the view on bacterial type I fatty acid synthesis and might inspire new strategies for inhibition of de novo fatty acid synthesis in M. tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / ultrastructure
  • Catalytic Domain
  • Cryoelectron Microscopy
  • Fatty Acid Synthases / chemistry*
  • Fatty Acid Synthases / ultrastructure
  • Models, Molecular
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / ultrastructure
  • Mycobacterium tuberculosis / enzymology*
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Structural Homology, Protein


  • Bacterial Proteins
  • Multienzyme Complexes
  • Fatty Acid Synthases

Associated data

  • PDB/4BJD
  • PDB/4BJE
  • PDB/4BJF
  • PDB/4BJG