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The intriguing chemistry and biology of soraphens

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Abstract

Covering: up to the end of 2018

Soraphens are a class of polyketide natural products discovered from the myxobacterial strain Sorangium cellulosum. The review is intended to provide an overview on the biosynthesis, chemistry and biological properties of soraphens, that represent a prime example to showcase the value of natural products as tools to decipher cell biology, but also to open novel therapeutic options. The prototype soraphen A is an inhibitor of acetyl coenzyme A carboxylase (ACC1/2), an enzyme that converts acetyl-CoA to malonyl-CoA and thereby controls essential cellular metabolic processes like lipogenesis and fatty acid oxidation. Soraphens illustrate how the inhibition of a single target (ACC1/2) may be explored to treat various pathological conditions: initially developed as a fungicide, efforts in the past decade were directed towards human diseases, including diabetes/obesity, cancer, hepatitis C, HIV, and autoimmune disease – and led to a synthetic molecule, discovered by virtual screening of the allosteric binding site of soraphen in ACC, that is currently in phase 2 clinical trials. We will summarize how structural analogs of soraphen A have been generated through extensive isolation efforts, genetic engineering of the biosynthetic gene cluster, semisynthesis as well as partial and total synthesis.

Graphical abstract: The intriguing chemistry and biology of soraphens

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Publication details

The article was received on 01 Feb 2019 and first published on 05 Apr 2019


Article type: Review Article
DOI: 10.1039/C9NP00008A
Citation: Nat. Prod. Rep., 2019, Advance Article

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    The intriguing chemistry and biology of soraphens

    A. Naini, F. Sasse and M. Brönstrup, Nat. Prod. Rep., 2019, Advance Article , DOI: 10.1039/C9NP00008A

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