Uncovering the formation and selection of benzylmalonyl-CoA from the biosynthesis of splenocin and enterocin reveals a versatile way to introduce amino acids into polyketide carbon scaffolds

Journal of the American Chemical Society
Chenchen ChangXudong Qu

Abstract

Selective modification of carbon scaffolds via biosynthetic engineering is important for polyketide structural diversification. Yet, this scope is currently restricted to simple aliphatic groups due to (1) limited variety of CoA-linked extender units, which lack aromatic structures and chemical reactivity, and (2) narrow acyltransferase (AT) specificity, which is limited to aliphatic CoA-linked extender units. In this report, we uncovered and characterized the first aromatic CoA-linked extender unit benzylmalonyl-CoA from the biosynthetic pathways of splenocin and enterocin in Streptomyces sp. CNQ431. Its synthesis employs a deamination/reductive carboxylation strategy to convert phenylalanine into benzylmalonyl-CoA, providing a link between amino acid and CoA-linked extender unit synthesis. By characterization of its selection, we further validated that AT domains of splenocin, and antimycin polyketide synthases are able to select this extender unit to introduce the phenyl group into their dilactone scaffolds. The biosynthetic machinery involved in the formation of this extender unit is highly versatile and can be potentially tailored for tyrosine, histidine and aspartic acid. The disclosed aromatic extender unit, amino acid-o...Continue Reading

References

Mar 1, 1970·Canadian Journal of Microbiology·G S BezansonL C Vining
Dec 18, 2002·Journal of Bacteriology·Masafumi KanekoSueharu Horinouchi
Jul 5, 2003·Chemical Communications : Chem Comm·Alison M HillRoger Segret
Jun 7, 2005·Journal of Bacteriology·Longkuan Xiang, Bradley S Moore
Sep 20, 2006·Proceedings of the National Academy of Sciences of the United States of America·Yolande A ChanMichael G Thomas
Mar 28, 2009·Journal of Medicinal Chemistry·Wendy K StrangmanWilliam Fenical
Apr 21, 2009·Natural Product Reports·Yolande A ChanMichael G Thomas
Jun 11, 2009·Angewandte Chemie·Christian Hertweck
Jan 21, 2010·Journal of Natural Products·Alessandra S EustáquioBradley S Moore
Nov 5, 2010·Nature·Weerawat RunguphanSarah E O'Connor
Dec 7, 2010·Current Opinion in Chemical Biology·Nicholas J Turner
Apr 21, 2011·Angewandte Chemie·Zhongli XuChristian Hertweck
Jun 15, 2011·Biochemistry·Guntur FibriansahAndy-Mark W H Thunnissen
Dec 6, 2011·Nature Chemical Biology·Nick QuadeRolf Müller
Feb 10, 2012·Journal of Natural Products·David J Newman, Gordon M Cragg
Sep 14, 2012·ACS Chemical Biology·Moriah SandyWenjun Zhang
Oct 23, 2012·ACS Chemical Biology·Irina KoryakinaGavin J Williams
Oct 30, 2012·Chembiochem : a European Journal of Chemical Biology·Irina Koryakina, Gavin J Williams
May 18, 2013·Organic & Biomolecular Chemistry·Irina KoryakinaGavin J Williams
May 31, 2013·Journal of the Royal Society, Interface·Briana J Dunn, Chaitan Khosla
Jul 11, 2013·Current Opinion in Structural Biology·Gavin J Williams
Nov 20, 2013·Journal of the American Chemical Society·Simone M Mantovani, Bradley S Moore
Jun 11, 2014·Acta Crystallographica. Section F, Structural Biology Communications·Lihan ZhangIkuro Abe
Jun 24, 2014·Expert Opinion on Drug Discovery·Simon E Ward, Paul Beswick
Dec 23, 2014·Nature Chemical Biology·Xuejun ZhuWenjun Zhang

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Citations

Nov 4, 2015·Journal of Industrial Microbiology & Biotechnology·Christopher C Ladner, Gavin J Williams
Mar 31, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chen HuGuang-Xiong Zhou
Nov 17, 2015·Natural Product Reports·Lauren Ray, Bradley S Moore
Oct 19, 2017·Nucleic Acids Research·Clara H EngJay D Keasling
Mar 11, 2016·F1000Research·Wenjun Zhang, Joyce Liu
Mar 16, 2017·Natural Product Reports·John W BluntMichèle R Prinsep
Jun 2, 2021·Archives of Microbiology·Karola SchühleJohann Heider

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