How nature incorporates sulfur and selenium into bioactive natural products

Carbohydrate-active enzyme (CAZyme) discovery and engineering via (Ultra)high-throughput screening

“…25,67 In fact, in Nature, carbon-sulfur bonds are generally cleaved enzymatically by elimination mechanisms. 68 Indeed, this is true also for the cleavage of thioglycosides which is nicely carried out by glycosidases in GH4, GH88, GH105, and GH109, which use elimination mechanisms, as well as by PLs. 25 By use of a thioglycoside substrate in which the chromogen is linked to the 1-thiosugar via a self-immolative linker, the authors were able to selectively identify unsaturated glucuronidases (of GH88) in a functional metagenomic screen.…”

Mechanistic Insights into the Selective C–S Bond Formation by P450 TleB

“…21−25 Various enzymes, including C−S bond-forming cyclases, 26−28 Stransferases, 29−33 nonheme iron enzymes, 34−40 radical Sadenosylmethionine enzymes, 41−43 and cytochrome P450 (CYP) monooxygenases, facilitate these reactions. 21,44,45 CYPs are versatile enzymes involved in the biosynthesis of natural or unnatural products. 46−55 Typical reactions include hydroxylation, 56−65 epoxidation desaturations, 66−72 C−C bond formation, 73−80 C−N bond formation, 75,76,81−88 C−S bond formation, 89−100 and C−O bond formation.…”

“…Enzymatic C–S bond formation offers advantages over chemical methods, in terms of mild reaction conditions, environmental friendliness, and high selectivity. − Various enzymes, including C–S bond-forming cyclases, − S-transferases, − nonheme iron enzymes, − radical S-adenosylmethionine enzymes, − and cytochrome P450 (CYP) monooxygenases, facilitate these reactions. ,, CYPs are versatile enzymes involved in the biosynthesis of natural or unnatural products. − Typical reactions include hydroxylation, − epoxidation desaturations, − C–C bond formation, − C–N bond formation, ,,− C–S bond formation, − and C–O bond formation. − Notably, TleB, a cytochrome P450 mon...…”

Biochemical and Structural Characterization of OvoATh2: A Mononuclear Nonheme Iron Enzyme from Hydrogenimonas thermophila for Ovothiol Biosynthesis

“…Besides their biological activities, the biosynthetic and mechanistic characterization of sulfur-containing natural products has sparked new chemistries and enzymology. − While l -cysteine or methionine commonly serves as sulfur sources in sulfur-containing peptides, the realm of sulfur incorporation chemistry extends far beyond peptide-based natural products. Exemplifying this versatility is ovothiol A and ergothioneine biosynthesis, which present elegant instances across various facets, , encompassing sulfur sources, aerobic vs anaerobic biosynthetic routes, exploration of diverse catalytic strategies, meticulous control over sulfur-transfer regioselectivity, and notably, the shared and distinct features between sulfur and selenium chemistries. − Over the past decade, four biosynthetic pathways for ergothioneine and one for ovothiol A have been elucidated. In the two aerobic pathways leading to ergothioneine, namely the mycobacterial pathway ( 4 → 4a → 4b → 2 transformations catalyzed by EgtB, EgtC, and EgtE enzymes, Scheme ) , and the fungal Neurospora crassa pathway ( 4 → 4b → 2 transformations catalyzed by Egt1 & Egt2/EgtE enzymes, Scheme ), , pivotal C–S bond formation steps are catalyzed by mononuclear nonheme iron enzymes.…”