Nonlinear Biosynthetic Assembly of Alpiniamide by a Hybrid cis/trans-AT PKS-NRPS.
ACS Chem Biol
; 15(4): 1067-1077, 2020 04 17.
Article
em En
| MEDLINE
| ID: mdl-32195572
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.
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1
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Sintases
/
Proteínas de Bactérias
/
Policetídeos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article