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 |
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 |
Citation Data
Cited 15 times in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
![]() |
Edit Item |