Unknown

Dataset Information

0

A combination of polyunsaturated fatty acid, nonribosomal peptide and polyketide biosynthetic machinery is used to assemble the zeamine antibiotics.


ABSTRACT: The zeamines are a unique group of antibiotics produced by Serratia plymuthica RVH1 that contain variable hybrid peptide-polyketide moieties connected to a common pentaamino-hydroxyalkyl chain. They exhibit potent activity against a broad spectrum of Gram-positive and Gram-negative bacteria. Here we report a combination of targeted gene deletions, high resolution LC-MS(/MS) analyses, in vitro biochemical assays and feeding studies that define the functions of several key zeamine biosynthetic enzymes. The pentaamino-hydroxyalkyl chain is assembled by an iterative multienzyme complex (Zmn10-13) that bears a close resemblance to polyunsaturated fatty acid synthases. Zmn14 was shown to function as an NADH-dependent thioester reductase and is proposed to release a tetraamino-hydroxyalkyl thioester from the acyl carrier protein domain of Zmn10 as an aldehyde. Despite the intrinsic ability of Zmn14 to catalyze further reduction of aldehydes to alcohols, the initially-formed aldehyde intermediate is proposed to undergo preferential transamination to produce zeamine II. In a parallel pathway, hexapeptide-monoketide and hexapeptide-diketide thioesters are generated by a hybrid nonribosomal peptide synthetase-polyketide synthase multienzyme complex (Zmn16-18) and subsequently conjugated to zeamine II by a stand-alone condensing enzyme (Zmn19). Structures for the resulting prezeamines were elucidated using a combination of high resolution LC-MS/MS and 1- and 2-D NMR spectroscopic analyses. The prezeamines are hypothesized to be precursors of the previously-identified zeamines, which are generated by the action of Zmn22, an acylpeptide hydrolase that specifically cleaves the N-terminal pentapeptide of the prezeamines in a post-assembly processing step. Thus, the zeamine antibiotics are assembled by a unique combination of nonribosomal peptide synthetase, type I modular polyketide synthase and polyunsaturated fatty acid synthase-like biosynthetic machinery.

SUBMITTER: Masschelein J 

PROVIDER: S-EPMC5811116 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

A combination of polyunsaturated fatty acid, nonribosomal peptide and polyketide biosynthetic machinery is used to assemble the zeamine antibiotics.

Masschelein Joleen J   Clauwers Charlien C   Awodi Ufedo R UR   Stalmans Karen K   Vermaelen Wesley W   Lescrinier Eveline E   Aertsen Abram A   Michiels Chris C   Challis Gregory L GL   Lavigne Rob R  

Chemical science 20141015 2


The zeamines are a unique group of antibiotics produced by <i>Serratia plymuthica</i> RVH1 that contain variable hybrid peptide-polyketide moieties connected to a common pentaamino-hydroxyalkyl chain. They exhibit potent activity against a broad spectrum of Gram-positive and Gram-negative bacteria. Here we report a combination of targeted gene deletions, high resolution LC-MS(/MS) analyses, <i>in vitro</i> biochemical assays and feeding studies that define the functions of several key zeamine bi  ...[more]

Similar Datasets

| S-EPMC3442147 | biostudies-literature
| S-EPMC8363725 | biostudies-literature
| S-EPMC4078802 | biostudies-other
| S-EPMC4646845 | biostudies-literature
| S-EPMC6525064 | biostudies-literature
| S-EPMC7143880 | biostudies-literature
| S-EPMC7762793 | biostudies-literature
| S-EPMC1482551 | biostudies-literature
| S-EPMC6689883 | biostudies-literature
| S-EPMC9811515 | biostudies-literature