Polyketide synthase chimeras reveal key role of ketosynthase domain in chain branching

ABSTRACT Biosynthesis of rhizoxin in _Burkholderia rhizoxinica_ affords an unusual polyketide synthase module with ketosynthase and branching domains that install the δ-lactone, conferring

antimitotic activity. To investigate their functions in chain branching, we designed chimeric modules with structurally similar domains from a glutarimide-forming module and a dehydratase.

Biochemical, kinetic and mutational analyses reveal a structural role of the accessory domains and multifarious catalytic actions of the ketosynthase. Access through your institution Buy or

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access 06 December 2023 ACCESSION CODES ACCESSIONS GENBANK/EMBL/DDBJ * CBW75249.1 * CCC21123.1 PROTEIN DATA BANK * 4KC5 REFERENCES * Hertweck, C. _Angew. Chem. Int. Ed._ 48, 4688–4716

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Perner for MS analyses and M. Poetsch for MALDI measurements. We are grateful for financial support by the International Leibniz Research School (to S.S.) and the Studienstiftung des

Deutschen Volkes (to D.H.). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology (HKI),

Jena, Germany Srividhya Sundaram, Daniel Heine & Christian Hertweck * Chair of Natural Product Chemistry, Friedrich Schiller University, Jena, Germany Christian Hertweck Authors *

Srividhya Sundaram View author publications You can also search for this author inPubMed Google Scholar * Daniel Heine View author publications You can also search for this author inPubMed 

Google Scholar * Christian Hertweck View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS S.S. and C.H. designed experiments; S.S. performed

genetic and biochemical experiments and analyzed data; D.H. synthesized substrates and reference compounds; and S.S. and C.H. wrote the manuscript. CORRESPONDING AUTHOR Correspondence to

Christian Hertweck. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary

Results, Supplementary Notes 1 and 2 and Supplementary Figures 1–10. (PDF 3399 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Sundaram, S., Heine,

D. & Hertweck, C. Polyketide synthase chimeras reveal key role of ketosynthase domain in chain branching. _Nat Chem Biol_ 11, 949–951 (2015). https://doi.org/10.1038/nchembio.1932

Download citation * Received: 07 July 2015 * Accepted: 28 August 2015 * Published: 19 October 2015 * Issue Date: December 2015 * DOI: https://doi.org/10.1038/nchembio.1932 SHARE THIS ARTICLE

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