Dithiolopyrrolone Natural Products

Isolation, Synthesis and Biosynthesis

Zhiwei Qin, Sheng Huang, Yi Yu, Hai Deng

Research output: Contribution to journalArticle

23 Citations (Scopus)
4 Downloads (Pure)

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 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.
Original languageEnglish
Pages (from-to)3970-3997
Number of pages28
JournalMarine Drugs
Volume11
Issue number10
DOIs
Publication statusPublished - 17 Oct 2013

Fingerprint

Biological Products
Multigene Family
Yersinia ruckeri
Pseudoalteromonas
Mupirocin
RNA
Anti-Bacterial Agents
Bacteria
Methyltransferases
Methicillin-Resistant Staphylococcus aureus
Gram-Negative Bacteria
Skeleton
Amides
Fishes
Parasites
Plasmids
Acids
holomycin
Growth
thiomarinol

Keywords

  • dithiolopyrrolone natural products
  • chemical isolation
  • total synthesis
  • biosynthesis
  • mode of action

Cite this

Dithiolopyrrolone Natural Products : Isolation, Synthesis and Biosynthesis. / Qin, Zhiwei; Huang, Sheng; Yu, Yi; Deng, Hai.

In: Marine Drugs, Vol. 11, No. 10, 17.10.2013, p. 3970-3997.

Research output: Contribution to journalArticle

Qin, Zhiwei ; Huang, Sheng ; Yu, Yi ; Deng, Hai. / Dithiolopyrrolone Natural Products : Isolation, Synthesis and Biosynthesis. In: Marine Drugs. 2013 ; Vol. 11, No. 10. pp. 3970-3997.
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