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Dithiolopyrrolone Natural Products: Isolation, Synthesis and Biosynthesis
Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education), School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UK
* Authors to whom correspondence should be addressed.
Received: 30 July 2013; in revised form: 25 September 2013 / Accepted: 26 September 2013 / Published: 17 October 2013
Abstract: Dithiolopyrrolones are a class of antibiotics that possess the unique pyrrolinonodithiole (4H-[1,2] dithiolo [4,3-b] pyrrol-5-one) skeleton linked to two variable acyl groups. To date, there are approximately 30 naturally occurring dithiolopyrrolone compounds, including holomycin, thiolutin, and aureothricin, and more recently thiomarinols, a unique class of hybrid marine bacterial natural products containing a dithiolopyrrolone framework linked by an amide bridge with an 8-hydroxyoctanoyl chain linked to a monic acid. Generally, dithiolopyrrolone antibiotics have broad-spectrum antibacterial activity against various microorganisms, including Gram-positive and Gram-negative bacteria, and even parasites. Holomycin appeared to be active against rifamycin-resistant bacteria and also inhibit the growth of the clinical pathogen methicillin-resistant Staphylococcus aureus N315. Its mode of action is believed to inhibit RNA synthesis although the exact mechanism has yet to be established in vitro. A recent work demonstrated that the fish pathogen Yersinia ruckeri employs an RNA methyltransferase for self-resistance during the holomycin production. Moreover, some dithiolopyrrolone derivatives have demonstrated promising antitumor activities. The biosynthetic gene clusters of holomycin have recently been identified in S. clavuligerus and characterized biochemically and genetically. The biosynthetic gene cluster of thiomarinol was also identified from the marine bacterium Pseudoalteromonas sp. SANK 73390, which was uniquely encoded by two independent pathways for pseudomonic acid and pyrrothine in a novel plasmid. The aim of this review is to give an overview about the isolations, characterizations, synthesis, biosynthesis, bioactivities and mode of action of this unique family of dithiolopyrrolone natural products, focusing on the period from 1940s until now.
Keywords: dithiolopyrrolone natural products; chemical isolation; total synthesis; biosynthesis; mode of action
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MDPI and ACS Style
Qin, Z.; Huang, S.; Yu, Y.; Deng, H. Dithiolopyrrolone Natural Products: Isolation, Synthesis and Biosynthesis. Mar. Drugs 2013, 11, 3970-3997.
Qin Z, Huang S, Yu Y, Deng H. Dithiolopyrrolone Natural Products: Isolation, Synthesis and Biosynthesis. Marine Drugs. 2013; 11(10):3970-3997.
Qin, Zhiwei; Huang, Sheng; Yu, Yi; Deng, Hai. 2013. "Dithiolopyrrolone Natural Products: Isolation, Synthesis and Biosynthesis." Mar. Drugs 11, no. 10: 3970-3997.