Sun et al. engineer Saccharomyces cerevisiae to convert glucose into indole-3-acetonitrile and multiple downstream tryptophan-derived indole compounds. By combining cytochrome P450 engineering with cofactor, endoplasmic reticulum, and precursor-supply and enzyme-mining strategies, they establish an artificial route toward 3,3′-diindolylmethane production and demonstrate the IAN as a branch point for expanding yeast biosynthesis.

Sun et al. engineer Saccharomyces cerevisiae to convert glucose into indole-3-acetonitrile and multiple downstream tryptophan-derived indole compounds. By combining cytochrome P450 engineering with co...

How allenes and alkynes are constructed in nature is poorly understood. Now, two fungal cytochrome P450 enzymes are shown to convert a common five-carbon prenyl group into four-carbon allene or alkyne motifs through oxidative C(sp2)-demethylation, establishing a biosynthetic carbon-editing strategy for generating these synthetically valuable functional groups.

Cytochrome P450 (CYP) monooxygenases are heme-thiolate enzymes that catalyze diverse oxidative transformations essential to metabolism, detoxification, and biosynthesis. While most CYPs rely on separa...

Cytochrome P450 (CYP) enzymes mediate the oxidative metabolism of most marketed drugs, making early prediction of their sites of metabolism (SoMs) essential for addressing metabolic liabilities. In th...

A titanium-based platform for dialkyl ether synthesis inspired by natural cytochrome P450 enzyme catalysis overcomes the limitations of traditional approaches, potentially paving the way for construct...

1,8-DHN is an important intermediate to form complex aromatic ring systems. Phenol-coupling reactions are important for the dimerization of two molecules. Here, we show that a fungal cytochrome P450 ...

1,8-DHN is an important intermediate to form complex aromatic ring systems. Phenol-coupling reactions are important for the dimerization of two molecules. Here, we show that a fungal cytochrome P450 enzyme catalyzes specific C─C bonds. ABSTRACT Dihydroxynaphthalene (DHN) derivatives are precursors of biologically important molecules, including melanin and perylenequinones (PQs). Biosynthesis of DHN-derived metabolites requires precise spatial control of radical reactions to form specific C─C or…

Published in Angewandte Chemie (International ed. in English)

Allenes and alkynes are important functional groups in chemical biology, yet their biosynthesis is poorly understood. Now, Liu et al. reveal that they form via oxidative C(sp2)-demethylation of the pr...

A semi-rationally engineered P450 disrupts the native radical transfer pathway to achieve highly selective B-ring C7β functionalization of pentacyclic triterpenoids. The installed C7β-OH handle supports chemoenzymatic synthesis of previously inaccessible B-ring-modified PT derivatives with potent antitumor activity, demonstrating the utility of enzyme engineering for the late-stage diversification of complex natural products. ABSTRACT Pentacyclic triterpenoids (PTs) feature a steroid-like privi…

Galantamine is a pharmaceutically relevant Amaryllidaceae alkaloid used for the treatment of Alzheimer's disease. Its structural complexity and low abundance in plants motivate the development of alternative manufacturing routes. Here, we established the first engineered yeast platform for the biocatalytic production of galantamine from 4OMe-norbelladine. Heterologous expression of the downstream pathway enzymes NtCYP96T6, NtNMT1, and NtAKR1 from Narcissus cv. Tete-a-Tete in Saccharomyces cerev…

Antiplatelet agents target the cyclooxygenase-1 (COX-1)/thromboxane A2 (TXA2) and adenosine diphosphate (ADP)-P2Y12 (cytochrome P450 2C19 [CYP2C19]-metabolized) platelet activation pathways, resultin....

The AOX pathway in Physcomitrium patens has high electron transport capacity and shows high complementarity with the cytochrome pathway. The combined activities of AOX and cytochrome-dependent respir...

The AOX pathway in Physcomitrium patens has high electron transport capacity and shows high complementarity with the cytochrome pathway. The combined activities of AOX and cytochrome-dependent respir...