Novel intermolecular iterative mechanism for biosynthesis of mycoketide catalyzed by a bimodular polyketide synthase
2008

New Mechanism for Mycoketide Biosynthesis by Polyketide Synthase

publication Evidence: high

Author Information

Author(s): Tarun Chopra, Srijita Banerjee, Gupta Sarika, Gitanjali Anand, Swadha Surolia, Avadhesha Roy, Rajendra P Mohanty, Debasisa Gokhale, Rajesh S

Primary Institution: National Institute of Immunology, New Delhi, India

Hypothesis

Can the PKS12 protein from Mycobacterium tuberculosis utilize a novel bimodular iterative mechanism for the biosynthesis of mycoketide?

Conclusion

The study provides evidence for a novel 'modularly iterative' mechanism of biosynthesis in polyketide synthases, enhancing our understanding of their catalytic versatility.

Supporting Evidence

  • PKS12 protein is involved in the biosynthesis of mannosyl-β-1-phosphomycoketide.
  • The study provides the first evidence for a novel 'modularly iterative' mechanism of biosynthesis.
  • PKS12 protein forms a supramolecular assembly mediated through specific interactions between the N- and C-terminus linkers.
  • Cell-free reconstitution of PKS12 enzymatic machinery demonstrated its ability to synthesize mycoketide.
  • Specificity of AT domains in PKS12 was confirmed through biochemical assays.

Takeaway

Scientists found a new way that a protein helps make important molecules in bacteria, which could help in creating new medicines.

Methodology

The study used biochemical, computational, mutagenic, analytical ultracentrifugation, and atomic force microscopy techniques to analyze the PKS12 protein.

Digital Object Identifier (DOI)

10.1371/journal.pbio.0060163

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