Abyssomicins from the South China Sea Deep‐Sea Sediment Verrucosispora sp.: Natural Thioether Michael Addition Adducts as Antitubercular Prodrugs

Regioselectivity of the Oxidative C–S Bond Formation in Ergothioneine and Ovothiol Biosyntheses

“…1 Biological sulfur transfer reactions can make use of either an ionic or a radical-type of reaction mechanism. For example, the thioether formation in lantibiotic biosynthesis is an ionic type of reaction that is accomplished by having thiolates as the direct nucleophiles.…”

“…2 Radical type C-S bond formation reactions are also well-documented. 1a, 3 Some of the examples are: the incorporation of the thiol-functional groups into biotin, 4 lipoate, 3a thiamine pyrophosphate, 5 molybdopterin cofactor, 6 cofactor biogenesis in galactose oxidase, 7 tRNA nucleotide thiolmethylation, 8 and thiazolidine ring formation catalyzed by isopenicillin N synthase. 9 For sulfur transfer reactions, two types of activated sulfur species have also been discovered, 10 which are persulfides R-S-SH and thiocarboxylates R-CO-SH.…”

“…11 Ergothioneine’s beneficial effects to human health are due to its unusual redox property, which favors predominantly the thione form ( 5b , Scheme 1A) and makes ergothioneine much more stable than most other natural thiols. 1c–d,11g Ergothioneine was isolated from ergot by Tanret in 1909, 12 and its biosynthetic gene cluster was reported by Seebeck in 2010 (Scheme 1A). 13 Ergothioneine biosynthesis starts from histidine methylation to trimethylated histidine (hercynine, 2 ), which is then oxidatively coupled with γ-glutamylcysteine (γ-Glu-Cys) to 3 .…”

Recent advances in the field of bioactive tetronates

“…As a result, the previously linear precursor is macrocyclized, and the cyclohexene ring is characteristically spiro-attached to the tetronic moiety. sea, South China) led to the isolation of the further abyssomicin derivatives J, K and L. 78 In 2011 the gene cluster for the biosynthesis of abyssomicin B, C and D was identied and later genomic investigations, together with feeding experiments with isotopically labelled precursors, revealed their polyketide origin. 79 Further structural details about the diversity of abyssomicins are depicted in Fig.…”

“…4) and its activity against M. tuberculosis was reported. 78 The study showed that the Michael acceptor system of abyssomicin C, which is essential for the antibiotic properties could be regenerated from the thioether-bridged abyssomicin dimer under oxidative conditions. It was therefore suggested that abyssomicin J could serve as a "natural prodrug".…”