A century of studying plant secondary metabolism—From “what?” to “where, how, and why?”

PLANT PHYSIOLOGY, Год журнала: 2024, Номер 195(1), С. 48 - 66

Опубликована: Янв. 2, 2024

Abstract Over the past century, early advances in understanding identity of chemicals that collectively form a living plant have led scientists to deeper investigations exploring where these molecules localize, how they are made, and why synthesized first place. Many small specific kingdom been termed secondary metabolites, despite fact can play primary essential roles structure, development, response environment. The 100 yr witnessed elucidation function, localization, biosynthesis selected metabolites. Nevertheless, many mysteries remain about vast diversity produced by plants their biology. From work characterizing unpurified extracts, modern integration ‘omics technology discover genes metabolite perception, research (bio)chemistry has knowledge with substantial benefits for society, including human medicine agricultural biotechnology. Here, we review history this offer suggestions future areas exploration. We also highlight some recently developed technologies leading ongoing advances.

Язык: Английский

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Reconstitution of early paclitaxel biosynthetic network

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 15, 2024

Abstract Paclitaxel is an anticancer therapeutic produced by the yew tree. Over last two decades, a significant bottleneck in reconstitution of early paclitaxel biosynthesis has been propensity heterologously expressed pathway cytochromes P450, including taxadiene 5α-hydroxylase (T5αH), to form multiple products. Here, we structurally characterize four new products T5αH, many which appear be over-oxidation primary mono-oxidized By tuning promoter strength for T5αH expression Nicotiana plants, observe decreased levels these proposed byproducts with concomitant increase accumulation taxadien-5α-ol, precursor, three-fold. This enables six step biosynthetic pathway, further show may function as metabolic network. Our result demonstrates that previously characterized Taxus genes can coordinatively produce key intermediates and serves crucial platform discovery remaining genes.

Язык: Английский

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Biosynthesis of the highly oxygenated tetracyclic core skeleton of Taxol

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 15, 2024

Abstract Taxol is a widely-applied anticancer drug that inhibits microtubule dynamics in actively replicating cells. Although minimum 19-step biosynthetic pathway has been proposed and 16 enzymes likely involved have characterized, stepwise reactions from the well-characterized di-oxygenated taxoids to tetracyclic core skeleton are yet be elucidated. Here, we uncover pathways for few tri-oxygenated via confirming critical reaction order of second third hydroxylation steps, unearth taxoid 9 α -hydroxylase catalyzing fourth hydroxylation, identify CYP725A55 oxetane ester formation cascade oxidation-concerted acyl rearrangement mechanism. After identifying acetyltransferase C7-OAc, producing highly-oxygenated 1 β -dehydroxybaccatin VI with elucidated its complete biosynthesis taxa-4(20),11(12)-diene-5 -ol achieved an engineered yeast. These systematic studies lay foundation elucidation Taxol.

Язык: Английский

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Classification, biosynthesis, and biological functions of triterpene esters in plants

Plant Communications, Год журнала: 2024, Номер 5(4), С. 100845 - 100845

Опубликована: Фев. 13, 2024

Triterpene esters comprise a class of secondary metabolites that are synthesised by decorating triterpene skeletons with series oxidation, glycosylation and acylation modifications. Many have been isolated identified important bioactivities, including applications in the pesticide, pharmaceutical cosmetic industries. They also play essential roles plant defense against pests, diseases, physical damage (as part cuticle) regulation root microorganisms. However, summary biosynthetic pathways biological functions is currently missing. Here, we classified into five categories accordance their found C-3 oxidation might impose significant effect on triterpenoid acylation. Fatty acid aromatic moieties were as common ligands present esters. We analysed synthesis-related acyltransferases (TEsACTs) pathway. By employing evolutionary classification BAHD (BAHD-ATs) serine carboxypeptidase-like (SCPL-ATs) Arabidopsis thaliana Oryza sativa criteria, 18 TEsACTs 11 species. Remarkably, all skeleton-related belong to clades IIIa I BAHD-ATs only one TEsACT from SCPL-AT family belongs CP-I. In general, provide comprehensive review ester providing foundation for subsequent studies bioactivities commercial applications, agricultural production disaster prevention.

Язык: Английский

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Pesticide reduction amidst food and feed security concerns in Europe

Nature Food, Год журнала: 2023, Номер 4(9), С. 746 - 750

Опубликована: Сен. 21, 2023

Abstract Recent studies have estimated the potential yield impacts of pesticide reductions in European Union. While these estimates guide policy design, they are often based on worst-case assumptions and rarely account for positive ecological feedbacks that would contribute to sustainable crop yields long term.

Язык: Английский

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Recent advances in triterpenoid pathway elucidation and engineering

Biotechnology Advances, Год журнала: 2023, Номер 68, С. 108214 - 108214

Опубликована: Июль 20, 2023

Язык: Английский

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Oxetane Ring Formation in Taxol Biosynthesis Is Catalyzed by a Bifunctional Cytochrome P450 Enzyme

Journal of the American Chemical Society, Год журнала: 2023, Номер 146(1), С. 801 - 810

Опубликована: Дек. 21, 2023

Taxol is a potent drug used in various cancer treatments. Its complex structure has prompted extensive research into its biosynthesis. However, certain critical steps, such as the formation of oxetane ring, which essential for activity, have remained unclear. Previous proposals suggested that follows acetylation taxadien-5α-ol. Here, we proposed ring formed by cytochrome P450-mediated oxidation events occur prior to C5 acetylation. To test this hypothesis, analyzed genomic and transcriptomic information Taxus species identify P450 candidates employed two independent systems, yeast (Saccharomyces cerevisiae) plant (Nicotiana benthamiana), their characterization. We revealed single enzyme, CYP725A4, catalyzes successive epoxidation events, leading ring. further showed both taxa-4(5)-11(12)-diene (endotaxadiene) taxa-4(20)-11(12)-diene (exotaxadiene) are precursors key intermediate, taxologenic oxetane, indicating potential existence multiple routes pathway. Thus, unveiled long-elusive step

Язык: Английский

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Bioprobe-RNA-seq-microRaman system for deep tracking of the live single-cell metabolic pathway chemometrics

Biosensors and Bioelectronics, Год журнала: 2024, Номер 261, С. 116504 - 116504

Опубликована: Июнь 14, 2024

Язык: Английский

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The evolutionary trajectories of specialized metabolites towards antiviral defense system in plants

Molecular Horticulture, Год журнала: 2024, Номер 4(1)

Опубликована: Янв. 12, 2024

Abstract Viral infections in plants pose major challenges to agriculture and global food security the twenty-first century. Plants have evolved a diverse range of specialized metabolites (PSMs) for defenses against pathogens. Although, PSMs-mediated plant-microorganism interactions been widely discovered, these are mainly confined plant-bacteria or plant-fungal interactions. PSM-mediated plant-virus interaction, however, is more complicated often due additional involvement virus spreading vectors. Here, we review classes PSMs their emerging roles involved antiviral resistances. In addition, evolutionary scenarios between plant, virus-transmitting vectors presented. These advancements comprehending biochemical language during not only lay foundation understanding potential co-evolution across life kingdoms, but also open gateway fundamental principles biological control strategies beyond. Graphical The putative co-evolutionary triad plant (PSM) mediated viruses insect This dynamic trio depicted through interplay represented by pink green arrows, signifying PSM bidirectional occurring virus, host vector.

Язык: Английский

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Toward an integrated omics approach for plant biosynthetic pathway discovery in the age of AI

Trends in Biochemical Sciences, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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