Frontiers in Plant Science, Год журнала: 2024, Номер 15

Опубликована: Ноя. 26, 2024

Natural products derived from medicinal plants are a class of compounds with extensive biological activities, playing crucial role in the pharmaceutical, food, and cosmetics industries. Due to their excellent physiological functions, increasing attention is being paid biosynthesis pathways plant natural (PNPs) (Kawatra et al., 2022;Halder Jha, 2023). However, as market demand continues grow, traditional harvesting extraction methods exert immense pressure on environment (Singh, In recent years, rapid advancement synthetic biology has offered new approaches for producing structurally complex bioactive small-molecule using biotechnology (Hesami Nevertheless, lack knowledge about biosynthetic significantly impedes largescale biomanufacturing plants. Unlike microorganisms, genes relatively dispersed across chromosomes, often efficient genetic manipulation systems, which hinders elucidation pathways.Recently, chemoproteomics based activity probes demonstrated great potential elucidating product (steviol glycosides, camptothecin, chalcomoracin, etc.), it enables identification functional proteins interacting substrates, thereby accelerating discovery (Li 2018;Zhou 2018;Gao 2020;Wong 2020;Zhang 2024) (Figure 1).Traditional have played advancing our understanding pathways, laying foundation emerging technologies like chemoproteomics. Gene knockout RNA interference (RNAi) methods, example, been widely used identify involved by observing phenotypic changes metabolite production when specific silenced (Zhao 2016). Additionally, multi-omics approaches, such transcriptomics, offer insights gene coexpression, though these can be limited need data analysis do not directly enzyme activities (Liu 2024a;Swamidatta Lichman, 2024). Heterologous expression, microbial enabled individual or clusters recreating outside native context (Lau Sattely, 2015;Hong 2022;Yang biochemical assays verify function may require large amounts purified protein, time-intensive process (Tatsis 2017). These while foundational, fall short dissecting within plants, where chemoproteomics, its activity-based annotation capabilities, offers distinct advantages. Consequently, applying technology comprehensively analyze only practical value but also holds strategic significance achieving through (Zhang 2022;Gao 2023;Liu 2023;Zhang 2023;Golubova 2024;Jiang 2024;Liu 2024b). Affinity specialized chemical tools isolate active enzymes samples, particularly those biosynthesis. typically consist binding moiety that targets enzyme's site, reactive tag capture covalent attachment after activation reporter detection.Effective affinity probe design requires specificity mimic stability conditions, controlled reactivity ensure selective durable (Parker Pratt, 2020;Fang 2021) 2). The primary advantage lies ability selectively target proteomes, bypassing purification manipulation. challenges non-specific complexity limit effectiveness (Tabana proven invaluable mapping shown studies synthesizing steviol glycosides other products. Steviol sweetening agents Stevia rebaudiana, studied due non-caloric sweeteners (Masand Recent research utilizing chemoproteomics-based strategy successfully identified UDP-glycosyltransferases (UGTs) SrUGT73E1, AtUGT73C1 AtUGT73C5, play pivotal catalyzing glycosylation form 2018;Wong 2020). use photoaffinity steviol, combined mass spectrometry, allowed researchers profile UGTs responsible final steps.This advances pathway novel platform glycosylation, enabling scalable production.Chalcomoracin, flavonoid isolated mulberry (Morus alba), synthesized highly unique flavin adenine dinucleotide (FAD)-dependent intermolecular Diels-Alder reaction. For this cycloaddition reaction was unknown, despite importance formation chalcomoracin's characteristic cyclohexene ring. enzyme, Morus alba Diels-Alderase (MaDA), intermediate (BIP)-based (Gao MaDA catalyzes the[4+2] high enantioselectivity, marking first stand-alone 2020;Gao characterization had remained inaccessible genomics transcriptomics clustering pathways.Camptothecin, an alkaloid potent anti-cancer properties, Camptotheca acuminata Ophiorrhiza pumila (Yang 2021). camptothecin long subject study, significant gap steps following strictosamide formation. A breakthrough came OpCYP716E111, epoxidase conversion epoxide. Using chemoproteomic approach, designed diazirine-based strictosamide, OpCYP716E111 proteome This fills critical underscores power uncover previously unknown metabolic processes.The discoveries surrounding highlight broad applicability field Traditional nature genes, making difficult pinpoint each step.Chemoproteomics circumvents issue targeting small molecule probes, allowing even non-model approach advantageous secondary metabolism organized into clusters, feature common systems rare Chemoproteomics advantages studying sensitivity detecting low-abundance without needing cloning protein expression steps. It distinguish between closely related isoforms multiple simultaneously, comprehensive view networks systems.These features make valuable biosynthesis.Furthermore, integration promise sustainable compounds. By identifying characterizing biosynthesis, reconstitute hosts, plant-derived 2023).Despite advantages, faces pathways. include optimization reliance high-quality spectrometry accurate identification. arise limitations affect efficiency specificity. Future advancements, improved selectivity omics technologies, hold overcoming obstacles enhancing approach's utility research.Chemoproteomics indispensable tool camptothecin. frontier research, key facilitating application biology. As will likely central unlocking full pharmaceutical industrial applications.MY: Conceptualization, Writing-original draft. MY, QY: Writing-review editing.

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