Glyceryl-S-acyl carrier protein as an intermediate in the biosynthesis of tetronate antibiotics

Chembiochem : a European Journal of Chemical Biology
Yuhui SunPeter F Leadlay

Abstract

The biosynthetic pathway to the unusual tetronate ring of certain polyketide natural products, including the antibiotics abyssomicin and tetronomycin (TMN) and the antitumour compound chlorothricin (CHL), is presently unknown. The gene clusters governing chlorothricin and tetronomycin biosynthesis both contain a gene encoding an atypical member of the FkbH family of enzymes, which has previously been shown to synthesise glyceryl-S-acyl carrier protein (ACP) as the first step in production of unusual extender units for modular polyketide biosynthesis. We show here that purified recombinant FkbH-like protein, Tmn16, from the TMN gene cluster catalyses the efficient transfer of a glyceryl moiety from D-1,3-bisphosphoglycerate (1,3-BPG) to either of the dedicated ACPs, Tmn7a and ChlD2, to form glyceryl-S-ACP, which directly implicates this compound as an intermediate in tetronate biosynthesis as well. Neither Tmn16 nor Tmn7a produced glyceryl-S-ACP when incubated, respectively, with analogous ACP and FkbH-like proteins from a known extender-unit pathway; this indicates a highly selective channelling of glycolytic metabolites into tetronate biosynthesis.

References

Mar 1, 1990·The Journal of Antibiotics·M HatsuH Yamamoto
Feb 1, 1982·The Journal of Antibiotics·C Keller-JuslénA von Wartburg
Sep 28, 2005·Journal of Industrial Microbiology & Biotechnology·Laura J WaltonGregory L Challis
Sep 20, 2006·Proceedings of the National Academy of Sciences of the United States of America·Yolande A ChanMichael G Thomas

Citations

Oct 16, 2012·Journal of the American Chemical Society·Qiongqiong WuWen Liu
Jan 19, 2010·Nature Chemical Biology·Yuhui SunPeter F Leadlay
Nov 17, 2015·Natural Product Reports·Lauren Ray, Bradley S Moore
Apr 23, 2013·Angewandte Chemie·Chompoonik KanchanabancaPeter F Leadlay
Jan 16, 2016·Chembiochem : a European Journal of Chemical Biology·Matthew J BertinWilliam H Gerwick
Aug 31, 2010·Bioorganic & Medicinal Chemistry Letters·Erick K LeggansRobert A Fecik
Dec 2, 2014·Journal of Natural Products·Michelle H Lacoske, Emmanuel A Theodorakis
Mar 13, 2008·Bioorganic & Medicinal Chemistry·Rainer Schobert, Andrea Schlenk
Jun 11, 2009·Angewandte Chemie·Christian Hertweck
Jul 3, 2009·Angewandte Chemie·Ivan Vilotijevic, Timothy F Jamison
Apr 12, 2008·Chembiochem : a European Journal of Chemical Biology·Yuliya DemydchukPeter F Leadlay
Oct 3, 2009·Microbiology·Yadira Dávila-MartínezIsabel M López-Lara
Aug 6, 2013·Chemistry & Biology·Yi-Ling DuKatherine S Ryan
Apr 21, 2009·Natural Product Reports·Yolande A ChanMichael G Thomas
Nov 29, 2008·Organic & Biomolecular Chemistry·Wendy L Kelly
Jun 27, 2014·Natural Product Reports·Laura ViewegRoderich D Süssmuth
Jun 14, 2018·Angewandte Chemie·Roy A MeodedJörn Piel
May 4, 2016·Journal of Bacteriology·Tomas Gverzdys, Justin R Nodwell
May 14, 2010·Natural Product Reports·Jörn Piel
Jul 6, 2014·Natural Product Reports·Gang LiMichael Spiteller
Feb 14, 2019·Natural Product Reports·Kuan Zheng, Ran Hong
Aug 26, 2016·Beilstein Journal of Organic Chemistry·Franziska Hemmerling, Frank Hahn
Apr 24, 2019·Marine Drugs·Alexander A Braddock, Emmanuel A Theodorakis

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