An Alternative Mechanism for C–C Desaturation Underscores a Dual-Controlled Mechanism for the Fate of Radical Intermediate in Iron(II)- and 2-(Oxo)glutarate-Dependent Oxygenase DfmD DOI
Xuan Zhang, Lanteng Wang, Jia Liu

и другие.

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Июнь 6, 2025

The C(sp3)-C(sp3) desaturation catalyzed by iron(II)- and 2-(oxo)glutarate-dependent(Fe/2OG) oxygenase is a key step in the biosynthesis modification of natural products. Similar to other C-H functionalization processes, reaction initiated active Fe(IV)-oxo species, which abstracts hydrogen atom from bond. However, Fe/2OG desaturase suppresses thermodynamically favored OH-rebound process. This enigmatic since substrate-cofactor disposition appears be favorable process involves activation followed OH rebound. To decipher mechanism, we studied here dehydrofosmidomycin DfmD, an enzyme that catalyzes product through desaturation, rearrangement, demethylation reactions. study employed biochemical, crystallographic, computational analysis reaction. Unlike sequential hydrogen-atom transfer (HAT) mechanism cation-dependent our reveals alternative for C-C desaturation. formation three-member ring intermediate oxaphosphiran. We found oxaphosphiran reduced barrier Additionally, H-bonding network disfavors pathway. As such, this dual action enables selective while bypassing hydroxylation highlights importance protein machinery as means controlling reactivity selectivity radical species.

Язык: Английский

The role and mechanisms of canonical and non-canonical tailoring enzymes in bacterial terpenoid biosynthesis DOI Creative Commons
Yuya Kakumu,

Ayesha Ahmed Chaudhri,

Eric J. N. Helfrich

и другие.

Natural Product Reports, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

This review explores recent insights into the roles and enzymatic mechanisms of canonical non-canonical tailoring enzymes in shaping modifying terpene hydrocarbon scaffolds during bacterial biosynthesis.

Язык: Английский

Процитировано

0

Characterization of an α‐ketoglutarate‐dependent oxygenase involved in converting 2‐(2‐phenylethyl)chromones into 2‐styrylchromones in agarwood DOI Open Access
Mingliang Zhang,

Jiangping Fan,

Zekun Zhang

и другие.

The Plant Journal, Год журнала: 2025, Номер 121(5)

Опубликована: Март 1, 2025

2-Phenylethylchromones (PECs) and 2-styrylchromones (SCs) are the primary components responsible for delightful fragrance bioactivity of agarwood, a highly valuable aromatic resinous heartwood. PECs derived from common precursor with diarylpentanoid skeleton (C6-C5-C6). However, biosynthesis SCs remains unclear. In this study, based on successful conversion PEC skeleton, rather than dehydrogenated diarylpentanoid, into by Aquilaria sinensis suspension cells, we demonstrated that double bond formation styryl group in occurs after creation not before step precursor. Through transcriptomic data mining, transient expression Nicotiana benthamiana A. identified new 2-oxoglutarate-dependent oxygenase (As2OG1) plays crucial role SCs. Further protein structure prediction mutagenesis studies, combined probing catalytic potential As2OG1 using chemically synthesized hydroxylated intermediates, suggested possibly uses diradical or carbocation to install bonds The results only provide insights molecular mechanism agarwood but also facilitate overproduction pharmaceutically important metabolic engineering approaches.

Язык: Английский

Процитировано

0

Concise Biosynthesis of Antifungal Papulacandins DOI
Chao Yu,

Niandi Zhang,

Jinmei Li

и другие.

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

We report the complete biosynthesis of antifungal papulacandins through heterologous expression and enzymatic assays. The papulacandin follows a convergent five-component strategy, involving linear polyketide chain that is synthesized installed to aryl-glucoside by synthase fused with C-terminal acyltransferase domain. formation challenging tricyclic benzannulated spiroketal core initiated C-glycosylation 5-(hydroxymethyl)resorcinol, followed spirocyclization catalyzed Fe(II)/α-ketoglutarate-dependent oxygenase PpcE.

Язык: Английский

Процитировано

0

Cytochrome P450-Catalyzed Allylic Oxidation of Pentalenene to 1-Deoxypentalenic Acid in Pentalenolactone Biosynthesis DOI Creative Commons
Jing Li, Chengde Zhang, Shiwen Wu

и другие.

Engineering Microbiology, Год журнала: 2025, Номер unknown, С. 100206 - 100206

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0

An Alternative Mechanism for C–C Desaturation Underscores a Dual-Controlled Mechanism for the Fate of Radical Intermediate in Iron(II)- and 2-(Oxo)glutarate-Dependent Oxygenase DfmD DOI
Xuan Zhang, Lanteng Wang, Jia Liu

и другие.

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Июнь 6, 2025

The C(sp3)-C(sp3) desaturation catalyzed by iron(II)- and 2-(oxo)glutarate-dependent(Fe/2OG) oxygenase is a key step in the biosynthesis modification of natural products. Similar to other C-H functionalization processes, reaction initiated active Fe(IV)-oxo species, which abstracts hydrogen atom from bond. However, Fe/2OG desaturase suppresses thermodynamically favored OH-rebound process. This enigmatic since substrate-cofactor disposition appears be favorable process involves activation followed OH rebound. To decipher mechanism, we studied here dehydrofosmidomycin DfmD, an enzyme that catalyzes product through desaturation, rearrangement, demethylation reactions. study employed biochemical, crystallographic, computational analysis reaction. Unlike sequential hydrogen-atom transfer (HAT) mechanism cation-dependent our reveals alternative for C-C desaturation. formation three-member ring intermediate oxaphosphiran. We found oxaphosphiran reduced barrier Additionally, H-bonding network disfavors pathway. As such, this dual action enables selective while bypassing hydroxylation highlights importance protein machinery as means controlling reactivity selectivity radical species.

Язык: Английский

Процитировано

0