N-acetyl-cysteinylated streptophenazines from Streptomyces

ABSTRACTHere, we describe two N-acetyl-cysteinylated streptophenazines (1 and 2) produced by soil-derived Streptomyces sp. ID63040 and identified through a metabolomic approach. These metabolites attracted our interest due to their low occurrence frequency in a large library of fermentation broth extracts and their consistent presence in biological replicates of the producer strain. The compounds were found to possess broad-spectrum antibacterial activity while exhibiting low cytotoxicity. The biosynthetic gene cluster from Streptomyces sp. ID63040 was found to be highly similar to the streptophenazine reference cluster in the MIBiG database, which originates from the marine Streptomyces sp. CNB-091. Compounds 1 and 2 were the main streptophenazine products from Streptomyces sp. ID63040 at all cultivation times, but were not detected in Streptomyces sp. CNB-091. The lack of obvious candidates for cysteinylation in the Streptomyces sp. ID63040 biosynthetic gene cluster suggests that the N-acetyl-cysteine moiety derives from cellular functions, most likely from mycothiol. Overall, our data represent an interesting example on how to leverage metabolomics for the discovery of new natural products and point out to the often-neglected contribution of house-keeping cellular functions to natural product diversification.Graphical abstract

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Identification of the Herboxidiene Biosynthetic Gene Cluster in Streptomyces chromofuscus ATCC 49982

Applied and Environmental Microbiology ◽

10.1128/aem.06904-11 ◽

2012 ◽

Vol 78 (6) ◽

pp. 2034-2038 ◽

Cited By ~ 19

Author(s):

Lei Shao ◽

Jiachen Zi ◽

Jia Zeng ◽

Jixun Zhan

Keyword(s):

Gene Cluster ◽

Genome Sequencing ◽

Fermentation Broth ◽

Biosynthetic Gene Cluster ◽

The Novel ◽

Biosynthetic Gene ◽

Content Type ◽

Minor Metabolite ◽

Streptomyces Chromofuscus ◽

A Minor

ABSTRACTThe 53-kb biosynthetic gene cluster for the novel anticholesterol natural product herboxidiene was identified inStreptomyces chromofuscusATCC 49982 by genome sequencing and gene inactivation. In addition to herboxidiene, a biosynthetic intermediate, 18-deoxy-herboxidiene, was also isolated from the fermentation broth ofS. chromofuscusATCC 49982 as a minor metabolite.

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Reconstitution of the Myxothiazol Biosynthetic Gene Cluster by Red/ET Recombination and Heterologous Expression in Myxococcus xanthus

Applied and Environmental Microbiology ◽

10.1128/aem.01503-06 ◽

2006 ◽

Vol 72 (12) ◽

pp. 7485-7494 ◽

Cited By ~ 64

Author(s):

Olena Perlova ◽

Jun Fu ◽

Silvia Kuhlmann ◽

Daniel Krug ◽

A. Francis Stewart ◽

...

Keyword(s):

Heterologous Expression ◽

Gene Cluster ◽

Myxococcus Xanthus ◽

Biosynthetic Gene Cluster ◽

Cosmid Library ◽

Biosynthetic Gene ◽

Producer Strain ◽

Metabolic Potential ◽

Stigmatella Aurantiaca ◽

One Step

ABSTRACT Although many secondary metabolites exhibiting important pharmaceutical and agrochemical activities have been isolated from myxobacteria, most of these microorganisms remain difficult to handle genetically. To utilize their metabolic potential, heterologous expression methodologies are currently being developed. Here, the Red/ET recombination technology was used to perform all required gene cluster engineering steps in Escherichia coli prior to the transfer into the chromosome of the heterologous host. We describe the integration of the complete 57-kbp myxothiazol biosynthetic gene cluster reconstituted from two cosmids from a cosmid library of the myxobacterium Stigmatella aurantiaca DW4-3/1 into the chromosome of the thus far best-characterized myxobacterium, Myxococcus xanthus, in one step. The successful integration and expression of the myxothiazol biosynthetic genes in M. xanthus results in the production of myxothiazol in yields comparable to the natural producer strain.

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Anacyclamide D8P, a prenylated cyanobactin from a Sphaerospermopsis sp. cyanobacterium

10.26434/chemrxiv.5346739.v1 ◽

2017 ◽

Cited By ~ 1

Author(s):

Joana Martins ◽

Niina Leikoski ◽

Matti Wahlsten ◽

Joana Azevedo ◽

Jorge Antunes ◽

...

Keyword(s):

Gene Cluster ◽

Cyclic Peptides ◽

Biosynthetic Gene Cluster ◽

The Novel ◽

Tyrosine Residue ◽

Biosynthetic Gene ◽

Post Translational Modification ◽

Biological Assays ◽

Mass Spectrometric Data ◽

Spectrometric Data

Cyanobactins are a family of linear and cyclic peptides produced through the post-translational modification of short precursor peptides. Anacyclamides are macrocyclic cyanobactins with a highly diverse sequence that are common in the genus Anabaena. A mass spectrometry-based screening of potential cyanobactin producers led to the discovery of a new prenylated member of this family of compounds, anacyclamide D8P (1), from Sphaerospermopsis sp. LEGE 00249. The anacyclamide biosynthetic gene cluster (acy) encoding the novel macrocyclic prenylated cyanobactin, was sequenced. Heterologous expression of the acy gene cluster in Escherichia coli established the connection between genomic and mass spectrometric data. Unambiguous establishment of the type and site of prenylation required the full structural elucidation of 1 using Nuclear Magnetic Resonance (NMR), which demonstrated that a forward prenylation occurred on the tyrosine residue. Compound 1 was tested in pharmacologically or ecologically relevant biological assays and revealed moderate antimicrobial activity towards the fouling bacterium Halomonas aquamarina CECT 5000.

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