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Nonlinear Biosynthetic Assembly of Alpiniamide by a Hybrid /-AT PKS-NRPS. | LitMetric

AI Article Synopsis

  • Alpiniamide A is a type of polyketide made by endophytic bacteria, previously thought to have a straightforward linear production method.
  • Recent research reveals that its synthesis is nonlinear, involving the creation of two halves that are later joined together.
  • This process uses different biosynthetic strategies for each half, suggesting a more complex operation of the enzymes involved than originally understood.

Article Abstract

Alpiniamide A is a linear polyketide produced by endophytic bacteria. Despite its relatively simple chemical structure suggestive of a linear assembly line biosynthetic construction involving a hybrid polyketide synthase-nonribosomal peptide synthetase enzymatic protein machine, we report an unexpected nonlinear synthesis of this bacterial natural product. Using a combination of genomics, heterologous expression, mutagenesis, isotope-labeling, and chain terminator experiments, we propose that alpiniamide A is assembled in two halves and then ligated into the mature molecule. We show that each polyketide half is constructed using orthogonal biosynthetic strategies, employing either - or -acyl transferase mechanisms, thus prompting an alternative proposal for the operation of this PKS-NRPS.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286424PMC
http://dx.doi.org/10.1021/acschembio.0c00081DOI Listing

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