The intriguing chemistry and biology of soraphens

authored by: Arun Naini, Florenz Sasse, Mark Brönstrup
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.
Organisation(s): Centre of Biomolecular Drug Research (BMWZ)
Section Chemical Biology
External Organisation(s): Helmholtz Centre for Infection Research (HZI)
German Center for Infection Research (DZIF)
Type: Review article
Journal: Natural product reports
Volume: 36
Pages: 1394-1411
No. of pages: 18
ISSN: 0265-0568
Publication date: 10.2019
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Biochemistry, Drug Discovery, Organic Chemistry
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Electronic version(s): https://doi.org/10.1039/c9np00008a (Access: Closed)