Nonlinear biosynthetic assembly of alpiniamide by a hybrid cis/trans-AT PKS-NRPS

Sigrist, Renata, Luhavaya, Hanna, McKinnie, Shaun M. K., Ferreira da Silva, Amanda, Jurberg, Igor D., Moore, Bradley S. and Gonzaga de Oliveira, Luciana 2020. Nonlinear biosynthetic assembly of alpiniamide by a hybrid cis/trans-AT PKS-NRPS. ACS Chemical Biology 15 (4) , pp. 1067-1077. 10.1021/acschembio.0c00081

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Abstract

Alpiniamide A is a linear polyketide produced by Streptomyces 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 cis- or trans-acyl transferase mechanisms, thus prompting an alternative proposal for the operation of this PKS-NRPS.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry
Publisher:	American Chemical Society
ISSN:	1554-8929
Date of Acceptance:	20 March 2020
Last Modified:	14 Nov 2022 16:06
URI:	https://orca.cardiff.ac.uk/id/eprint/153715

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