The intriguing chemistry and biology of soraphens. Issue 10 (5th April 2019)

• Record Type: Journal Article
• Authors: Naini, Arun; Sasse, Florenz; Brönstrup, Mark
• Is Part Of: Natural product reports. Volume 36:Issue 10(2019)
• Page Start: 1394
• Page End: 1411
• Publication Date: 2019-04-05
• Subjects: Natural products -- Periodicals; Produits naturels -- Périodiques; 547.7
• DOI: 10.1039/c9np00008a
• Languages: English
• ISSNs: 0265-0568

Abstract

Abstract : Soraphens, discovered from the myxobacterial strain Sorangium cellulosum, have intrigued chemists and biologists due to their diverse biological effects mediated by the potent inhibition of acetyl CoA carboxylase. 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.