Two of a Kind-The Biosynthetic Pathways of Chlorotonil and Anthracimycin

ACS Chemical Biology
Katrin JungmannRolf Müller

Abstract

Chlorotonil A is a novel polyketide isolated from the myxobacterium Sorangium cellulosum So ce1525 that features a unique gem-dichloro-1,3-dione moiety. It exhibits potent bioactivity, most notably against the problematic malaria pathogen Plasmodium falciparum in the nanomolar range. In addition, strong antibacterial and moderate antifungal activity were determined. The outstanding biological activity of chlorotonil A as well as its unusual chemical structure triggered our interest in elucidating its biosynthesis, a prerequisite for alteration of the scaffold by synthetic biology approaches. This endeavor was facilitated by a recent report describing the strikingly similar structure of anthracimycin from a marine streptomycete, a compound of considerable interest due to its potent antibacterial activity. In this study, we report the identification and characterization of the chlorotonil A biosynthetic gene cluster from So ce1525 and compare it with that for anthracimycin biosynthesis. Access to both gene clusters allowed us to highlight commonalities between the two pathways and revealed striking differences, some of which can plausibly explain the structural differences observed between these intriguing natural products.

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Citations

Feb 10, 2016·Current Opinion in Chemical Biology·Srividhya Sundaram, Christian Hertweck
Dec 23, 2015·Natural Product Reports·Eric J N Helfrich, Jörn Piel
Sep 9, 2015·ACS Chemical Biology·Silke Alt, Barrie Wilkinson
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Dec 3, 2016·Natural Product Reports·J HerrmannR Müller
Nov 2, 2019·AMB Express·Jérémy DomergueAnne Zaparucha
Nov 12, 2018·Journal of Industrial Microbiology & Biotechnology·Je Won Park, Yeo Joon Yoon
Mar 16, 2017·Natural Product Reports·John W BluntMichèle R Prinsep
Nov 21, 2020·Organic & Biomolecular Chemistry·Jamshid Amiri MoghaddamChristine Beemelmanns
May 7, 2021·Journal of the American Chemical Society·Mengting LiuYi Tang
Sep 5, 2018·ACS Chemical Biology·Greg J DodgeJanet L Smith
Aug 29, 2021·Pharmaceutics·Mudasir Ahmad BhatArif Tasleem Jan

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