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Post Polyketide Synthase Carbon-Carbon Bond Formation in Type-II PKS-Derived Natural Products from Streptomyces venezuelae

Research output: Contribution to Journal/MagazineJournal articlepeer-review

  • Andrew W Robertson
  • Jeanna M MacLeod
  • Logan W MacIntyre
  • Stephanie M Forget
  • Steven R Hall
  • Leah G Bennett
  • Hebelin Correa
  • Russell G Kerr
  • Kerry B Goralski
  • David L Jakeman
<mark>Journal publication date</mark>16/02/2018
<mark>Journal</mark>Journal of Organic Chemistry
Issue number4
Number of pages15
Pages (from-to)1876-1890
Publication StatusPublished
<mark>Original language</mark>English


Polyketide synthase (PKS) derived natural products are biosynthesized by head-to-tail addition of acetate and malonate extender units resulting in linear extended-polyketide chains. Despite the well-documented structural diversity associated with PKS-derived natural products, C-C chain branching deviating from the usual linear pattern is relatively rare. Herein, type-II PKS angucyclic natural products containing a hemiaminal functionality were identified and proposed as the parent of a series of C-C-branched analogues. These C-C linked acetate or pyruvate branching units were located at the α-positions on the extended polyketide chains of jadomycins incorporating 3- and 4-aminomethylbenzoic acids. Labeling studies utilizing [1-13C]-d-glucose provided mechanistic evidence that the C-C bond formation occurred as a result of a previously unidentified post-PKS processing, additional to the enzymes encoded within the biosynthetic gene cluster. Selected compounds were evaluated in cytotoxic or antimicrobial assays.