Matthew McConnachie, Tuan-Anh Minh Nguyen, Truc Kim, Trinh-Don Nguyen, Thu-Thuy T. Dang
{"title":"From data to discovery: leveraging big data in plant natural products biosynthesis research","authors":"Matthew McConnachie, Tuan-Anh Minh Nguyen, Truc Kim, Trinh-Don Nguyen, Thu-Thuy T. Dang","doi":"10.1111/tpj.70288","DOIUrl":"https://doi.org/10.1111/tpj.70288","url":null,"abstract":"<p>Plant natural products or specialized metabolites play a vital role in drug discovery and development, with many clinically important derivatives such as the anticancer drugs topotecan (derived from the natural alkaloid camptothecin) and etoposide (derived from the natural polyphenol podophyllotoxin). Remarkable advances in understanding plant natural product metabolism have been achieved at an unprecedented pace over the past 15 years. The integration of high-throughput technologies in genomics, transcriptomics, and metabolomics has generated vast datasets that provide a more comprehensive understanding of plant metabolism. Additionally, advances in computational tools, machine learning, and data analytics have played a crucial role in processing and interpreting the massive amounts of newly available data, enabling researchers to uncover intricate regulatory networks and identify key components of biosynthetic pathways. This review navigates the evolving landscape of plant biosynthetic pathway elucidation accelerated by innovative multidisciplinary strategies that capitalize on big data. We highlight recent advances in plant-specialized biosynthesis that illustrate how big data are increasingly leveraged to unravel the complexities of plant metabolism.</p>","PeriodicalId":233,"journal":{"name":"The Plant Journal","volume":"122 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tpj.70288","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yue Yang, Jun Wei, Yu Wang, Mingkun Chen, Song Li, Ziyi Han, Yu Duan, Yaping Xu, Hongmei Sun, Houhua Li
{"title":"Auxin signaling mediated embryogenic cell formation during the early stage of somatic embryogenesis in Malus domestica “Gala”","authors":"Yue Yang, Jun Wei, Yu Wang, Mingkun Chen, Song Li, Ziyi Han, Yu Duan, Yaping Xu, Hongmei Sun, Houhua Li","doi":"10.1111/tpj.70287","DOIUrl":"https://doi.org/10.1111/tpj.70287","url":null,"abstract":"<div>\u0000 \u0000 <p>Embryogenic cell formation is a prerequisite for somatic embryogenesis (SE) in plants. Auxin signaling is indispensable for the initiation of embryogenic cell formation. However, the mechanism of auxin signaling that regulates this process in apple remains unclear. In this study, the <i>MdAUX/IAA7.1</i> and <i>MdARF5</i> genes were identified as key auxin signaling regulators in the early stage of SE through RNA sequencing and RT-qPCR in <i>Malus domestica</i> “Gala.” <i>MdARF5</i> significantly promoted embryogenic cell formation and shortened the induction cycle of SE in transgenic overexpression assays. When <i>MdARF5</i> was knocked out, the explants could not form somatic embryos even when stimulated with exogenous auxin. Through RNA sequencing analysis of <i>MdARF5</i>-overexpressing lines and transgenic assays, <i>MdLBD41</i> was identified as the key gene that regulates SE and responds to <i>MdARF5.</i> In response to auxin signaling, the MdARF5 protein directly binds to the promoter of <i>MdLBD41</i> to activate its transcription, thereby promoting SE in apples. MdAUX/IAA7.1 interacts with the MdARF5 protein without auxin signaling, inhibiting the downstream transcription of <i>MdLBD41</i>, and thereby negatively regulating SE in apples. In conclusion, our results elucidate the mechanism of <i>MdAUX/IAA7.1</i> and <i>MdARF5</i> genes responding to auxin and <i>MdARF5,</i> promoting the embryogenic cell formation by mediating the positive regulation of <i>MdLBD41</i> expression.</p>\u0000 </div>","PeriodicalId":233,"journal":{"name":"The Plant Journal","volume":"122 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The time machine: feedback loops, post-transcriptional regulation, and environmental integration in the plant circadian oscillator","authors":"Stacey L. Harmer","doi":"10.1111/tpj.70275","DOIUrl":"https://doi.org/10.1111/tpj.70275","url":null,"abstract":"<div>\u0000 \u0000 <p>Daily rhythms in physiology are obvious and widespread. While for millennia it was thought that these cycles represent passive responses to environmental cycles, we now recognize that many of them are governed by circadian oscillators. In plants, these cell-autonomous oscillators regulate daily processes such as photosynthesis, organ growth, and hormone production, as well as seasonal transitions like flowering. Furthermore, the circadian system gates plant responses to biotic and abiotic stresses, modulating susceptibility to pathogens and environmental extremes in a time-of-day-dependent manner. Variants of circadian clock genes have been repeatedly selected during crop domestication and improvement, highlighting the importance of the circadian system to plants and its relevance for agriculture. Here, I review the history of circadian studies in plants and summarize our current understanding of the molecular nature of the circadian oscillator. I also discuss how this complex network both responds to and is buffered against changes in the environment. Next, I examine how circadian oscillators differ between various tissues and how their activities are coordinated throughout the plant body. Finally, I discuss emerging directions, such as ways in which this understanding can be applied to crop improvement in the face of climate change.</p>\u0000 </div>","PeriodicalId":233,"journal":{"name":"The Plant Journal","volume":"122 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pavel Trávníček, Jan Ponert, Marcos Vinicius Dantas-Queiroz, Zuzana Chumová
{"title":"Integrating genome-wide traits and multi-loci phylogeny to investigate orchid evolution—A case study on Pleurothallidinae","authors":"Pavel Trávníček, Jan Ponert, Marcos Vinicius Dantas-Queiroz, Zuzana Chumová","doi":"10.1111/tpj.70281","DOIUrl":"https://doi.org/10.1111/tpj.70281","url":null,"abstract":"<p>Rapidly radiated groups are usually accompanied by unclear lineage and taxa delineation, which complicates their better understanding in terms of biodiversity, evolutionary processes, and taxonomic treatment. The most species-rich orchid subtribe, Pleurothallidinae, exemplifies an extremely diverse group with a complex evolutionary history associated with Andean orography. Here we combined multi-loci phylogeny reconstruction (HybSeq), genome-wide traits (inferred by flow cytometry), spatial analyses, and biogeography to investigate the evolutionary intricacy of one clade of Pleurothallidinae orchids. To achieve deep insights, we performed multiple species tree reconstruction approaches with the implementation of custom scripts to reveal sources of topological discrepancies and alternative evolutionary scenarios. The phylogeny clearly resolves the delimitation of the main evolutionary lineages corresponding to the accepted genera, with the exception of the genus <i>Specklinia</i>, which is divided into three distinct monophyletic lineages whose taxonomic treatment is proposed. Genome-wide characters (especially genome size) show an association with precipitation seasonality in a geographical context, and partial endoreplication, a unique character of orchids, is geographically restricted to the Andes, Central America, and the Caribbean. Specifically, the Andean region exemplifies the prevalence of bigger genome size and higher GC content, resulting from a higher proportion of species with partial endoreplication. The Andean origin of the clade was also revealed by biogeographic analysis. Our comprehensive approach has provided deep insights into the evolution of this clade and may be a useful tool for unraveling the intricate evolutionary history of similarly complex lineages.</p>","PeriodicalId":233,"journal":{"name":"The Plant Journal","volume":"122 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tpj.70281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonathan Scarfe, Darius Kosmützky, R. Ellen R. Nisbet
{"title":"A game of tag: A review of protein tags for the successful detection, purification and fluorescence labelling of proteins expressed in microalgae","authors":"Jonathan Scarfe, Darius Kosmützky, R. Ellen R. Nisbet","doi":"10.1111/tpj.70272","DOIUrl":"https://doi.org/10.1111/tpj.70272","url":null,"abstract":"<p>Recombinant proteins play a crucial role in both fundamental research and biotechnology. In the laboratory, recombinant proteins are used in a myriad of ways, including to label cells, localize proteins and isolate complexes. In the clinic, antibody-based therapeutics can dramatically increase cancer survival rates, while virus-like particles (VLPs) are being developed as next-generation vaccines. These innovations have escalated demands for biopharmaceutical recombinant proteins. However, in traditional systems (e.g. mammalian and microbial) the expression of recombinant proteins can be prohibitively expensive. One sustainable, low-cost solution is to use a microalgal-based expression system, such as <i>Chlamydomonas reinhardtii, Phaeodactylum tricornutum</i>, <i>Chlorella</i> sp., <i>Haematococcus pluvialis</i> or <i>Nannochloropsis gaditana</i>. Tools for microalgal protein expression are developing rapidly. Yet our understanding of recombinant protein expression and purification in microalgal systems lags that of traditional systems. Here, we review the impact of commonly used affinity and epitope tags (e.g. Polyhistidine-tag, Strep-tag II, HA-tag and FLAG-tag) on recombinant protein detection, purification and biofunctionality in microalgae. Additionally, we review fluorescent protein tags (such as GFP, mVenus, DsRed and mCherry) and protease cleavage sites, including ‘self-cleaving’ 2A peptides. Finally, we provide guidance on experimental design to enhance the likelihood of successfully expressing recombinant proteins in microalgae.</p>","PeriodicalId":233,"journal":{"name":"The Plant Journal","volume":"122 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tpj.70272","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Grain under pressure: Harnessing biochemical pathways to beat drought and heat in wheat","authors":"Itsuhiro Ko, Tyler Chapman, Taras Nazarov, Ruth Uwugiaren, Andrei Smertenko, Niharika Nonavinakere Chandrakanth, Dylan Oates","doi":"10.1111/tpj.70253","DOIUrl":"https://doi.org/10.1111/tpj.70253","url":null,"abstract":"<p>Erratic climate patterns represent a remarkable challenge to global food security, particularly affecting staple cereal crops of which wheat (<i>Triticum aestivum</i>) plays a critical role in annual agricultural production globally. It has been shown that over the last four decades, wheat cultivation has faced an escalating vulnerability to a variety of abiotic stresses, including heat and drought. These stressors not only decrease overall yield but also compromise grain quality, leading to reduced soluble starch content, higher protein content, altered grain texture, diminished end-use quality, and various other undesirable changes. With climate change projections indicating an intensification and higher frequency of heat and drought conditions in the future, urgent action is needed to develop resilient wheat varieties. Achieving this goal relies on a comprehensive understanding of the molecular responses to environmental shifts during successive stages of reproduction. Here we discuss three types of critical biochemical pathways responsible for sustaining starch biosynthesis in both source and sink tissues under adverse environmental conditions during grain development: (i) signaling network and cross-talk between ABA and SnRK pathways; (ii) transcriptional changes of the enzymes and signaling components; and (iii) inhibition of enzyme activity through temperature-induced misfolding. While summarizing the current knowledge, we also highlight critical factors contributing to the deterioration of grain quality and propose potential strategies for enhancing the resilience of starch biosynthesis in wheat grain.</p>","PeriodicalId":233,"journal":{"name":"The Plant Journal","volume":"122 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tpj.70253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junhong Liu, Cuicui Du, Ping Zhao, Shiwei Yang, Hui Zhong, Shoujian Zang, Binghua Wu, Zhiqiang Zhang, Jun Luo, Youxiong Que, Hengbo Wang
{"title":"The interplay between ScSWEET11 promoters and Paracidovorax avenae effectors regulate resistance in sugarcane","authors":"Junhong Liu, Cuicui Du, Ping Zhao, Shiwei Yang, Hui Zhong, Shoujian Zang, Binghua Wu, Zhiqiang Zhang, Jun Luo, Youxiong Que, Hengbo Wang","doi":"10.1111/tpj.70255","DOIUrl":"https://doi.org/10.1111/tpj.70255","url":null,"abstract":"<div>\u0000 \u0000 <p>Red stripe, caused by the bacterial pathogen <i>Paracidovorax avenae</i>, poses a significant threat to the sugarcane industry. The Sugar Will Eventually be Exported Transporter (SWEET) gene family participates in plant–pathogen interactions. However, the specific mechanism underlying the interaction between SWEETs and the red stripe pathogen remains unclear. In this study, 17, 21, and 25 members of the SWEET gene family were identified from <i>Saccharum spontaneum</i>, <i>S. officinarum</i>, and <i>Saccharum</i> spp. hybrid, respectively. They were phylogenetically divided into four clades. Four members in clade III, especially <i>ScSWEET11</i>, showed significantly different expression patterns between red stripe-resistant and susceptible sugarcane varieties. Subsequently, the <i>ScSWEET11</i> gene was isolated and overexpressed in tobacco, resulting in significant lesions when infected with <i>P. avenae</i> (<i>Pa</i>), and there was no substantial difference in lesion area compared to wild-type tobacco. Heterologous expression of <i>ScSWEET11</i> demonstrated sucrose transport activity in yeast sugar transport mutants. Besides, pScSWEET11_I and pScSWEET11_II, the two types of SWEET11 promoters in <i>Saccharum</i>, were mined and found to originate from <i>S. spontaneum</i> and <i>S. officinarum</i>, respectively. Interestingly, both types of promoters were observed in the susceptible cultivar, while there was only pScSWEET11_II in the resistant one. Notably, the activity of pScSWEET11_I was much higher than that of pScSWEET11_II, particularly under ABA and <i>P. avenae</i> stress conditions. Yeast one-hybrid, dual-luciferase reporter, and transient overexpression assays indicated that the interaction between PaXopQ, PaXopAU, PaXopF2, and pScSWEET11_I led to more susceptibility by promoting the <i>ScSWEET11</i> expression, while that between PaAvrRxo1, PaXopAU, and pScSWEET11_II resulted in higher resistance through suppressing the <i>ScSWEET11</i> expression. Collectively, this study provided a good understanding of the regulatory network for the red stripe pathogen invading the host, offering a valuable research basis for molecular breeding of disease-resistant sugarcane.</p>\u0000 </div>","PeriodicalId":233,"journal":{"name":"The Plant Journal","volume":"122 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lu Zhao, Xiaomei Ma, Wenxue Ma, Zhaoming Wang, Dong Luo, Qiang Zhou, Wenxian Liu, Longfa Fang, Jingbo Jin, Iain R. Searle, Zhipeng Liu
{"title":"MsPYL6 and MsPYL9 improves drought tolerance by regulating stomata in alfalfa (Medicago sativa)","authors":"Lu Zhao, Xiaomei Ma, Wenxue Ma, Zhaoming Wang, Dong Luo, Qiang Zhou, Wenxian Liu, Longfa Fang, Jingbo Jin, Iain R. Searle, Zhipeng Liu","doi":"10.1111/tpj.70265","DOIUrl":"https://doi.org/10.1111/tpj.70265","url":null,"abstract":"<div>\u0000 \u0000 <p>Severe drought stress can significantly reduce alfalfa production, and the phytohormone abscisic acid plays a central role in responses to abiotic stress. As abscisic acid receptors, the PYRABACTIN RESISTANCE 1/PYR1-LIKE/ABA-binding REGULATORY COMPONENT OF ABA RECEPTOR (PYR1/PYL/RCAR) family constitutes a critical component of the ABA signaling pathway, mediating adaptive responses and protecting plants under drought conditions. In this study, nine <i>MsPYL</i> genes were identified in alfalfa, and their expression levels were found to be significantly upregulated in response to ABA and drought stress. The overexpression of <i>MsPYL</i> genes in both <i>Arabidopsis thaliana</i> and alfalfa significantly improved drought tolerance. Among the <i>MsPYL</i> family genes, functional analysis of <i>MsPYL6</i> and <i>MsPYL9</i> revealed that both genes enhanced water-use efficiency by reducing leaf stomatal density, promoting stomatal closure, and decreasing transpiration rates when overexpressed. In contrast, the RNAi plants exhibited the opposite phenotypes, with increased stomatal density and higher transpiration rates. Furthermore, overexpression plants exhibited reduced malondialdehyde content and lower reactive oxygen species levels, indicating enhanced cellular stability under stress. Additionally, transcriptome analysis showed that drought-responsive genes related to antioxidant defense, stomatal regulation, and photosynthesis were more abundant in drought-treated OE plants and less abundant in RNAi plants. Interaction analysis revealed that all MsPYL proteins could interact with at least one MsPP2CA, indicating a conserved interaction pattern in ABA signaling. These findings confirm that <i>MsPYLs</i> play a crucial role in the ABA signaling pathway by modulating the expression of downstream drought-tolerant genes, thereby enabling alfalfa to effectively respond to drought stress conditions.</p>\u0000 </div>","PeriodicalId":233,"journal":{"name":"The Plant Journal","volume":"122 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cytokinin-mediated repression of anthocyanin biosynthesis in banana fruits","authors":"Ruchika Rajput, Shivi Tyagi, Kumar Anchal, Samar Singh, Ashverya Laxmi, Prashant Misra, Ashutosh Pandey","doi":"10.1111/tpj.70267","DOIUrl":"https://doi.org/10.1111/tpj.70267","url":null,"abstract":"<div>\u0000 \u0000 <p>Anthocyanins are pigments responsible for vibrant plant colors and play vital roles in plant physiology. This study compares two banana cultivars, Grand Naine (GN) and Red Banana (RB), which exhibit significant differences in anthocyanin pigmentation. Transcriptomic profiling of peel (PL) and pulp (PP) tissues revealed cytokinin-responsive type-B response regulators (RRs), MaRR_B9 and MaRR_B12, as key modulators of anthocyanin biosynthesis. Cytokinin treatment of PP tissues increased the expression of <i>MaRR_B9</i> and <i>MaRR_B12</i>, while significantly reducing the expression of <i>dihydroflavanol reductase</i> (<i>MaDFR1</i>, <i>MaDFR2</i>) and <i>anthocyanidin synthase (MaANS</i>) genes along with anthocyanin content. Through a combination of physiological, molecular, and biochemical analyses, we demonstrate that MaRR_B9 and MaRR_B12 exert direct regulatory control over key structural genes of anthocyanin biosynthesis, <i>MaDFRs</i> and <i>MaANS</i>. Additionally, a type B-RRs motif (AGATT) was identified in the promoter regions of <i>MaDFR2</i> and <i>MaANS</i>, suggesting that MaRRs might directly regulate the transcription of <i>MaDFR2</i> and <i>MaANS</i>. MaRR_B9 and MaRR_B12 interact with the promoters of <i>MaDFR2</i> and <i>MaANS</i>, repressing these genes <i>in vivo</i>. Overexpression of <i>MaRR_B9</i> and <i>MaRR_B12</i> in banana fruits leads to a reduction in anthocyanin content, notably the cyanidin derivative, accompanied by altered expression patterns of <i>MaDFRs</i> and <i>MaANS</i>. Thus, the present study identifies MaRR_B9 and MaRR_B12 as novel regulators of anthocyanin biosynthesis in banana and provides further evidence that the cytokinin regulatory network modifies anthocyanin accumulation in plants. In conclusion, our findings reveal new molecular targets, in the form of MaRRs, for the genetic optimization aimed at enhancing anthocyanin content, stress resilience, and nutritional value in crop plants.</p>\u0000 </div>","PeriodicalId":233,"journal":{"name":"The Plant Journal","volume":"122 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lukas Ernst, Hesham M.B. Sayed, Ahmed Hassanin, Rebekka Moegenburg, Tomke Meents, Hui Lyu, David Kaufholdt, Mehdi D. Davari, Ludger Beerhues, Benye Liu, Islam El-Awaad
{"title":"Reverse prenylation in plants by non-canonical aromatic prenyltransferases","authors":"Lukas Ernst, Hesham M.B. Sayed, Ahmed Hassanin, Rebekka Moegenburg, Tomke Meents, Hui Lyu, David Kaufholdt, Mehdi D. Davari, Ludger Beerhues, Benye Liu, Islam El-Awaad","doi":"10.1111/tpj.70268","DOIUrl":"https://doi.org/10.1111/tpj.70268","url":null,"abstract":"<p>Reverse-prenylated phenolic compounds are an abundant class of bioactive plant natural products. Hyperixanthone A, an inhibitor of multidrug-resistant <i>Staphylococcus aureus</i>, is a polyprenylated xanthone carrying two forward geminal and one reverse prenyl group. Although prenyltransferases responsible for the forward prenylations were identified, the final reverse prenylation reaction remained elusive. No plant enzyme catalyzing reverse prenylation of an aromatic carbon has been described so far. Here we use metabolic profiling and transcriptomic information from <i>Hypericum perforatum</i> and <i>H. sampsonii</i> to identify homologous enzymes involved in the formation of reverse-prenylated xanthones and characterize their functions using <i>in vitro</i>, <i>in vivo</i>, and <i>in silico</i> approaches. The identified enzymes are non-canonical UbiA-type prenyltransferases, which surprisingly catalyze both forward and reverse prenylations with different regioselectivities. Reconstruction of the enzyme cascade in <i>Saccharomyces cerevisiae</i> and <i>Nicotiana benthamiana</i> confirmed reverse-prenylated hyperixanthone A as the major product. Molecular modeling and docking simulations supported by site-directed mutagenesis suggest two distinct binding modes, which enable forward and reverse prenylations and provide a rationale for the preferred catalysis of the reverse prenyl transfer reaction. The identification of reverse prenylation augments the repertoire of reactions catalyzed by membrane-bound UbiA-type plant aromatic prenyltransferases. The insights also provide a new tool for the biotechnological modification of pharmaceutically valuable natural products.</p>","PeriodicalId":233,"journal":{"name":"The Plant Journal","volume":"122 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tpj.70268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}