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.
Subject(s)
Bacterial Proteins/metabolism , Peptide Synthases/metabolism , Polyketides/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Catalytic Domain , Genomics , Multigene Family , Peptide Synthases/chemistry , Peptide Synthases/genetics , Protein Domains , Streptomyces/genetics , Streptomyces/metabolismABSTRACT
The whole-genome sequence of Streptomyces sp. strain CBMAI 2042, an endophytic actinobacterium isolated from Citrus sinensis branches, is described. The strain has the ability to inhibit the growth of Xylella fastidiosa and other human pathogens. In silico analysis highlighted the presence of nonribosomal peptide and polyketide synthases, revealing promising antibiotic assembly lines.