bryA: An unusual modular polyketide synthase gene from the uncultivated bacterial symbiont of the marine bryozoan Bugula neritina

Mark Hildebrand, Laura E. Waggoner, Haibin Liu, Sebastian Sudek, Scott Allen, Christine Anderson, David H. Sherman, Margo Haygood

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

"Candidatus Endobugula sertula," the uncultivated bacterial symbiont of Bugula neritina, is the proposed source of the bryostatin family of anticancer compounds. We cloned a large modular polyketide synthase (PKS) gene complex from "Candidatus Endobugula sertula" and characterized one gene, bryA, which we propose is responsible for the initial steps of bryostatin biosynthesis. Typical PKS domains are present. However, acyltransferase domains are lacking in bryA, and β-ketoacyl synthase domains of bryA cluster with those of PKSs with discrete, rather than integral, acyltransferases. We propose a model for biosynthesis of the bryostatin D-lactate starter unit by the bryA loading module, utilizing atypical domains homologous to FkbH, KR, and DH. The bryA gene product is proposed to synthesize a portion of the pharmacologically active part of bryostatin and may be useful in semisynthesis of clinically useful bryostatin analogs.

Original languageEnglish (US)
Pages (from-to)1543-1552
Number of pages10
JournalChemistry and Biology
Volume11
Issue number11
DOIs
StatePublished - Nov 1 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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    Hildebrand, M., Waggoner, L. E., Liu, H., Sudek, S., Allen, S., Anderson, C., Sherman, D. H., & Haygood, M. (2004). bryA: An unusual modular polyketide synthase gene from the uncultivated bacterial symbiont of the marine bryozoan Bugula neritina. Chemistry and Biology, 11(11), 1543-1552. https://doi.org/10.1016/j.chembiol.2004.08.018