Myxochelin- and Pseudochelin-Derived Lipoxygenase Inhibitors from a Genetically Engineered Myxococcus xanthus Strain.

@article{Sester2019MyxochelinAP,
  title={Myxochelin- and Pseudochelin-Derived Lipoxygenase Inhibitors from a Genetically Engineered Myxococcus xanthus Strain.},
  author={Angela Sester and Lea Winand and Simona Pace and Wolfgang Hiller and Oliver Werz and Markus Nett},
  journal={Journal of natural products},
  year={2019}
}
Precursor-directed biosynthesis was used to introduce selected aryl carboxylic acids into the pseudochelin pathway, which had recently been assembled in Myxococcus xanthus. Overall, 14 previously undescribed analogues of the natural products myxochelin B and pseudochelin A were generated and structurally characterized. A subset of 10 derivatives together with their parental molecules were evaluated for their activity toward human 5-lipoxygenase. This testing revealed pseudochelin A as the most… 

Expanding the Myxochelin Natural Product Family by Nicotinic Acid Containing Congeners

The combined evaluation of metabolome and genome data covering myxobacteria supports the notion that the new myxochelin congeners reported here are in fact frequent side products of the known myx Rochelin A biosynthetic pathway in myXobacteria.

Discovery, Biosynthesis and Biological Activity of a Succinylated Myxochelin from the Myxobacterial Strain MSr12020

The isolation, structure elucidation and a proposed biosynthesis of the new congener myxochelin B-succinate from the terrestrial myxobacterial strain MSr12020, featuring a succinyl decoration at its primary amine group are reported.

The Discovery and Biosynthesis of Nicotinic Myxochelins from an Archangium sp. SDU34.

Two new compounds are reported, myxochelins N (1) and O (2), that are nicotinic paralogs of myxochelin A, from the terrestrial myxobacterium Archangium sp.

Biosynthetic Plasticity Enables Production of Fluorinated Aurachins

The plasticity of the aurachin biosynthesis pathway with regard to using fluoro‐ and chloroanthranilic acids, which are not abundant in the bacterial producers of these quinolone antibiotics, is explored.

Mutasynthesis of Physostigmines in Myxococcus xanthus.

This work produced a series of physostigmine analogues with altered specificity and toxicity profiles in the heterologous host Myxococcus xanthus, including the promising drug candidate phenserine, which was previously accessible only by total synthesis.

Production of Multiple Talaroenamines from Penicillium malacosphaerulum via One-Pot/Two-Stage Precursor-Directed Biosynthesis.

This work demonstrated the one-pot/two-stage precursor-directed biosynthesis could improve substrate acceptance leading to the production of diverse talaroenamines.

Secondary Metabolism of Predatory Bacteria

This chapter will summarize recent key findings in the field and provide a comprehensive overview on the biosynthetic capabilities of two model predators, namely Bdellovibrio bacteriovorus and Myxococcus xanthus.

A Disturbed Siderophore Transport Inhibits Myxobacterial Predation

The results showed that the obstruction of siderophores transport decreased myxobacterial predation ability through the downregulation of lytic enzyme genes, especially outer membrane vesicle (OMV)-specific proteins.

Supercritical Fluid Extraction Enhances Discovery of Secondary Metabolites from Myxobacteria.

Extracts generated with SFE showed increased antimicrobial activities including the presence of activities not explained by known myxobacterial secondary metabolites, highlighting the advantage of SFE for bioactivity-guided isolation.

Bioengineering of Anti‐Inflammatory Natural Products

An outline of the biotechnological methods used to derivatize anti‐inflammatory natural products, including precursor‐directed biosynthesis, mutasynthesis, combinatorial biosynthetic, as well as whole‐cell and in vitro biotransformation are presented.

References

SHOWING 1-10 OF 15 REFERENCES

Harnessing Enzymatic Promiscuity in Myxochelin Biosynthesis for the Production of 5‐Lipoxygenase Inhibitors

To clarify whether the iron‐chelating properties of myxochelin A are responsible for this activity, several analogues of this compound were generated in the native producer Pyxidicoccus fallax by precursor‐directed biosynthesis.

Myxochelins target human 5-lipoxygenase.

Extracts of the predatory myxobacterium Pyxidicoccus fallax HKI 727 showed antiproliferative effects on leukemic K-562 cells, and Pharmacological testing revealed human 5-lipoxygenase as a molecular target of the myxochelins.

Myxochelin A, a new iron-chelating compound from Angiococcus disciformis (Myxobacterales). Production, isolation, physico-chemical and biological properties.

The new substance showed weak activity against some bacteria and could be markedly increased up to 44 mg/liter by fermentation at low iron concentrations (10(-7) M FeCl3).

Myxochelin‐Inspired 5‐Lipoxygenase Inhibitors: Synthesis and Biological Evaluation

By expanding the diaminoalkane linker of the two aromatic residues it was possible to generate a myxochelin derivative with superior activity against 5‐lipoxygenase in intact cells.

Novel Insights into Siderophore Formation in Myxobacteria

Biochemical and genetic studies described here further clarify myxochelin biosynthesis and reveal that although the organization of the biosynthetic genes is completely different, the biosynthesis is most probably extremely similar.

Absolute Configuration and Antitumor Activity of Myxochelin A Produced by Nonomuraea pusilla TP-A0861†

Both enantiomers of myxochelin A showed remarkable inhibitory effects on the invasion of murine colon 26-L5 carcinoma cells at non-cytotoxic concentrations.

The myxochelin iron transport regulon of the myxobacterium Stigmatella aurantiaca Sg a15.

The biosynthetic gene cluster of the myxochelin-type iron chelator was cloned from Stigmatella aurantiaca Sg a15 and characterized. This catecholate siderophore was only known from two other

Hyalachelins A-C, unusual siderophores isolated from the terrestrial myxobacterium Hyalangium minutum.

Three new siderophores, termed hyalachelins A-C (1-3), were isolated from the terrestrial myxobacterium Hyalangium minutum. Their structures were determined by 2D NMR and HR-MS/MS experiments, and

Functional characterization of a novel arachidonic acid 12S‐lipoxygenase in the halotolerant bacterium Myxococcus fulvus exhibiting complex social living patterns

It is found that M. fulvus expresses a catalytically active intracellular lipoxygenase that converts arachidonic acid and other polyunsaturated fatty acids enantioselectively to the corresponding n‐9 hydroperoxy derivatives.