Deciphering chemical logic of fungal natural product biosynthesis through heterologous expression and genome mining

Natural Product Reports, Год журнала: 2022, Номер 40(1), С. 89 - 127

Опубликована: Сен. 20, 2022

Covering: 2010 to 2022Heterologous expression of natural product biosynthetic gene clusters (BGCs) has become a widely used tool for genome mining cryptic pathways, bottom-up investigation enzymes, and engineered biosynthesis new variants. In the field fungal products, heterologous complete pathway was first demonstrated in tenellin

Язык: Английский

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Pretrichodermamide A Biosynthesis Reveals the Hidden Diversity of Epidithiodiketopiperazines

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(18)

Опубликована: Март 3, 2023

Fungal epidithiodiketopiperazines (ETPs) possess large structural diversity and complexity due to modifications of the cyclodipeptide skeleton. Elucidation biosynthetic pathway pretrichodermamide A (1) in Trichoderma hypoxylon revealed a flexible catalytic machinery multiple enzymes for generating ETP diversity. Seven tailoring encoded by tda cluster are involved 1 biosynthesis, that is, four P450s TdaB TdaQ 1,2-oxazine formation, TdaI C7'-hydroxylation, TdaG C4, C5-epoxidation, two methyltransferases TdaH C6'- TdaO C7'-O-methylation, reductase TdaD furan opening. Gene deletions led identification 25 novel ETPs, including 20 shunt products, indicating promiscuity Tda enzymes. Particularly, accept various substrates catalyze regiospecific reactions at different stages biosynthesis. Our study not only uncovers hidden library alkaloids, but also helps understand chemical natural products manipulation.

Язык: Английский

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Decoration of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) with N‐oxides increases the T₁ relaxivity of Gd‐complexes

ChemistryOpen, Год журнала: 2024, Номер 13(7)

Опубликована: Янв. 15, 2024

Abstract High complex stability and longitudinal relaxivity of Gd‐based contrast agents are important requirements for magnetic resonance imaging (MRI) because they ensure patient safety contribute to measurement sensitivity. Charged zwitterionic Gd 3+ ‐complexes the well‐known chelator 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) provide an excellent basis development safe sensitive agents. In this report, we describe synthesis DOTA‐NOx, a DOTA derivative with four N ‐oxide functionalities via “click” functionalization tetraazide DOTAZA. The resulting complexes Gd‐DOTA‐NOx Eu‐DOTA‐NOx stable compounds in aqueous solution. NMR‐spectroscopic characterization revealed high excess twisted square antiprismatic (TSAP) coordination geometry over (SAP). was found be r 1 =7.7 m −1 s (1.41 T, 37 °C), unusually value comparable weight. We attribute steric influence ordering effect on outer sphere water molecules surrounding generated by strongly hydrated groups. Moreover, against transchelation EDTA (200 eq) period 36 h, it has similar vitro cell toxicity as clinically used DOTA‐based GBCAs.

Язык: Английский

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Surface Grafted N‐Oxides have Low‐Fouling and Antibacterial Properties

Advanced Materials Interfaces, Год журнала: 2023, Номер 10(35)

Опубликована: Сен. 14, 2023

Abstract Low‐fouling materials are often generated by surface zwitterionization with polymers. In this context, poly‐ N ‐oxides have recently attracted considerable attention as biomimetic stealth coatings low protein adsorption. Herein, study reports that can be grafted from plasma‐activated plastic base materials. The resulting hydrophilic surfaces low‐fouling properties in bacterial suspensions and suppress the formation of biofilms. Moreover, efficient antibacterial activity against Gram‐negative Gram‐positive bacteria caused release reactive oxygen species is observed. latter effect specific for polymeric most likely triggered a reductive activation ‐oxide functionality presence bacteria. contrast to other zwitterionic polymers, combine thus (stealth) activity. bioactive groups regenerated after use common oxidative disinfectants. Poly‐ attractive many unique combined mechanism action.

Язык: Английский

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Discovery of cadinane sesquiterpenoids as GOT1 inhibitors from Penicillium sp. HZ-5

Bioorganic Chemistry, Год журнала: 2025, Номер 157, С. 108303 - 108303

Опубликована: Фев. 25, 2025

Язык: Английский

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Hydroxylamine natural products

˜The œAlkaloids. Chemistry and biology/˜The œalkaloids. Chemistry and biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Synthetic Biology in Natural Product Biosynthesis

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

Synthetic biology has played an important role in the renaissance of natural products research during post-genomics era. The development and integration new tools have transformed workflow product discovery engineering, generating multidisciplinary interest field. In this review, we summarize recent developments biosynthesis from three different aspects. First, advances bioinformatics, experimental, analytical to identify associated with predicted biosynthetic gene clusters (BGCs) will be covered. This followed by extensive review on heterologous expression bacterial, fungal plant organisms. native host-independent paradigm identification, pathway characterization, enzyme is where synthetic most prominent role. Lastly, strategies engineer pathways for structural diversification complexity generation discussed, including assembly-line megasynthase precursor-directed modification, combinatorial biosynthesis.

Язык: Английский

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Dihydroartemisinic acid dehydrogenase-mediated alternative route for artemisinin biosynthesis

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 24, 2025

Dihydroartemisinic acid (DHAA) converts into antimalarial drug artemisinin (ART) by auto-oxidation. High production of artemisinic (AA) has been achieved fermentation engineered Saccharomyces cerevisiae, and AA can be converted ART through DHAA chemical synthesis. However, there is no enzyme reported to catalyze the conversion DHAA. Here, we report a dihydroartemisinic dehydrogenase (AaDHAADH) from Artemisia annua L, which catalyzes bidirectional between An optimized mutant AaDHAADH (P26L) obtained site-directed mutagenesis its activity toward 2.82 times that original gene. De novo synthesis in S. cerevisiae using targeted gene (P26L). Furthermore, 3.97 g/L 5 L bioreactor. The discovery provides more convenient efficient alternative route for biosynthesis.

Язык: Английский

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Organocatalytic (3+3)-cycloaddition of ortho-substituted phenyl nitrones with aryl cyclopropane carbaldehydes: a facile access to enantioenriched 1,2-oxazinanes

Chemical Communications, Год журнала: 2023, Номер 59(74), С. 11133 - 11136

Опубликована: Янв. 1, 2023

The first asymmetric (3+3)-cycloaddition of ortho-substituted phenyl nitrones with aryl cyclopropane carbaldehydes has been demonstrated by secondary amine catalysts. While the other ortho-substituents gave 1,2-oxazinanes, ortho-hydroxy ones provided a novel class tetrahydrochromeno-1,2-oxazine cores via rare 1,3-aryl migration, followed cyclization. An unusual type approach was also recognized.

Язык: Английский

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Natural products with 1,2-oxazine scaffold: occurrence, chemical diversity, bioactivity, synthesis, and biosynthesis

Natural Product Reports, Год журнала: 2023, Номер 40(12), С. 1874 - 1900

Опубликована: Янв. 1, 2023

This review summarizes the chemical family of natural products with 1,2-oxazine scaffold, focusing on their source organisms, structural diversities, bioactivities, synthesis, and biosynthesis.

Язык: Английский

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