Unusual Acetylation–Elimination in the Formation of Tetronate Antibiotics

Authors

  • Chompoonik Kanchanabanca,

    1. Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA (UK)
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    • These authors contributed equally to this work.

  • Dr. Weixin Tao,

    1. Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuchan 430071 (P.R.China)
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    • These authors contributed equally to this work.

  • Dr. Hui Hong,

    1. Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA (UK)
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  • Yajing Liu,

    1. Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuchan 430071 (P.R.China)
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  • Dr. Frank Hahn,

    1. Institute of Organic Chemistry, Leibniz Universität Hannover, Callinstrasse 22, 30167 Hannover (Germany)
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  • Dr. Markiyan Samborskyy,

    1. Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA (UK)
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  • Prof. Dr. Zixin Deng,

    1. Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuchan 430071 (P.R.China)
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  • Prof. Dr. Yuhui Sun,

    Corresponding author
    1. Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuchan 430071 (P.R.China)
    • Yuhui Sun, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuchan 430071 (P.R.China)

      Peter F. Leadlay, Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA (UK)

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  • Prof. Dr. Peter F. Leadlay

    Corresponding author
    1. Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA (UK)
    • Yuhui Sun, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuchan 430071 (P.R.China)

      Peter F. Leadlay, Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA (UK)

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  • This research was supported by grants from the Biotechnology and Biological Sciences Research Council (BBSRC BB/D018943/1), and the 973 and 863 programs from the Ministry of Science and Technology, the National Natural Science Foundation of China, the Ministry of Education. C.K. acknowledges a stipend from the Higher Education Commission of Thailand, W.T. acknowledges funding from the China Postdoctoral Science Foundation (CPSF 2012M521461), and F.H. funding as an EU Marie Curie Postdoctoral Fellow. F.H. is an Emmy Noether Fellow of the Deutsche Forschungsgemeinschaft, and P.F.L. is a Research Awardee of the Alexander von Humboldt Foundation. We thank Prof. Dr. R. D. Süssmuth and Dr. F. Huang for helpful discussions.

Abstract

original image

The identity and reactivity of the intermediates in agglomerin biosynthesis were established and the respective roles of the acetyltransferase Agg4 and the eliminating enzyme Agg5 identified (see scheme). It is proposed that enzymes homologous to Agg4 and Agg5 carry out the dehydration steps in all spirotetronate biosynthetic pathways. If this proves correct, it may assist engineering of these pathways.

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