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1.
Cell ; 185(3): 513-529.e21, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35120663

RESUMO

The human gut microbiota resides within a diverse chemical environment challenging our ability to understand the forces shaping this ecosystem. Here, we reveal that fitness of the Bacteroidales, the dominant order of bacteria in the human gut, is an emergent property of glycans and one specific metabolite, butyrate. Distinct sugars serve as strain-variable fitness switches activating context-dependent inhibitory functions of butyrate. Differential fitness effects of butyrate within the Bacteroides are mediated by species-level variation in Acyl-CoA thioesterase activity and nucleotide polymorphisms regulating an Acyl-CoA transferase. Using in vivo multi-omic profiles, we demonstrate Bacteroides fitness in the human gut is associated together, but not independently, with Acyl-CoA transferase expression and butyrate. Our data reveal that each strain of the Bacteroides exists within a unique fitness landscape based on the interaction of chemical components unpredictable by the effect of each part alone mediated by flexibility in the core genome.


Assuntos
Microbioma Gastrointestinal , Metaboloma , Polissacarídeos/metabolismo , Acil Coenzima A/metabolismo , Sequência de Aminoácidos , Aminoácidos de Cadeia Ramificada/metabolismo , Bacteroidetes/efeitos dos fármacos , Bacteroidetes/genética , Bacteroidetes/crescimento & desenvolvimento , Butiratos/química , Butiratos/farmacologia , Coenzima A-Transferases/química , Coenzima A-Transferases/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Variação Genética/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Metaboloma/efeitos dos fármacos , Metaboloma/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Especificidade da Espécie , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética , Transcrição Gênica/efeitos dos fármacos
2.
Cell ; 166(4): 881-893, 2016 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-27518563

RESUMO

Classically, hormones elicit specific cellular responses by activating dedicated receptors. Nevertheless, the biosynthesis and turnover of many of these hormone molecules also produce chemically related metabolites. These molecules may also possess hormonal activities; therefore, one or more may contribute to the adaptive plasticity of signaling outcomes in host organisms. Here, we show that a catabolite of the plant hormone abscisic acid (ABA), namely phaseic acid (PA), likely emerged in seed plants as a signaling molecule that fine-tunes plant physiology, environmental adaptation, and development. This trait was facilitated by both the emergence-selection of a PA reductase that modulates PA concentrations and by the functional diversification of the ABA receptor family to perceive and respond to PA. Our results suggest that PA serves as a hormone in seed plants through activation of a subset of ABA receptors. This study demonstrates that the co-evolution of hormone metabolism and signaling networks can expand organismal resilience.


Assuntos
Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Sesquiterpenos/metabolismo , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , NADP/metabolismo , Transdução de Sinais
3.
Cell ; 159(5): 977-978, 2014 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-25416938

RESUMO

Understanding nitrogen metabolism in plants holds promise for future agricultural improvements. Chellamuthu et al. now identify a feedback regulation in plant nitrogen metabolism through glutamine sensing. This mechanism appears to be conserved from algae to flowering plants with a few surprising exceptions.


Assuntos
Glutamina/metabolismo , Plantas/metabolismo
4.
Plant J ; 118(6): 2169-2187, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38558472

RESUMO

Genome-wide association studies (GWAS) are an effective approach to identify new specialized metabolites and the genes involved in their biosynthesis and regulation. In this study, GWAS of Arabidopsis thaliana soluble leaf and stem metabolites identified alleles of an uncharacterized BAHD-family acyltransferase (AT5G57840) associated with natural variation in three structurally related metabolites. These metabolites were esters of glucuronosylglycerol, with one metabolite containing phenylacetic acid as the acyl component of the ester. Knockout and overexpression of AT5G57840 in Arabidopsis and heterologous overexpression in Nicotiana benthamiana and Escherichia coli demonstrated that it is capable of utilizing phenylacetyl-CoA as an acyl donor and glucuronosylglycerol as an acyl acceptor. We, thus, named the protein Glucuronosylglycerol Ester Synthase (GGES). Additionally, phenylacetyl glucuronosylglycerol increased in Arabidopsis CYP79A2 mutants that overproduce phenylacetic acid and was lost in knockout mutants of UDP-sulfoquinovosyl: diacylglycerol sulfoquinovosyl transferase, an enzyme required for glucuronosylglycerol biosynthesis and associated with glycerolipid metabolism under phosphate-starvation stress. GGES is a member of a well-supported clade of BAHD family acyltransferases that arose by duplication and neofunctionalized during the evolution of the Brassicales within a larger clade that includes HCT as well as enzymes that synthesize other plant-specialized metabolites. Together, this work extends our understanding of the catalytic diversity of BAHD acyltransferases and uncovers a pathway that involves contributions from both phenylalanine and lipid metabolism.


Assuntos
Aciltransferases , Arabidopsis , Fenilacetatos , Aciltransferases/genética , Aciltransferases/metabolismo , Arabidopsis/genética , Arabidopsis/enzimologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Estudo de Associação Genômica Ampla , Fenilacetatos/metabolismo
5.
J Adv Nurs ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041430

RESUMO

AIM: A skin tear (ST) is a common skin injury that is often misdiagnosed or overlooked. This study examined the current state of nurses' ST knowledge and its influencing factors. DESIGN: A national cross-sectional survey combined with a quantitative analysis was used to provide evidence of poor ST knowledge among nurses and its influencing factors. METHODS: An electronic questionnaire survey was conducted among 1293 nurses from 32 hospitals in 18 provinces across China, including a General Information Questionnaire, ST Knowledge Assessment Instrument (OASES) and a Self-directed Learning Competence Scale for Nurses (SLCS-N). RESULTS: The mean OASES score was 9.51 ± 3.15, with a score rate of 47.55%. Pearson's correlation analysis showed positive correlations, ranging from none to strong, between every dimension in the OASES and from strong to extremely strong between every dimension in the SLCS-N. Multivariate analysis revealed multiple independent factors influencing ST knowledge, such as hospital tier, specialized nurses in wound/ostomy/incontinence care, participation in training for wound/ostomy/incontinence management, willingness to undergo ST training, self-assessed grade in ST care and the degree of emphasis of managers. CONCLUSION: ST knowledge status was generally poor among nurses nationwide. Managers should establish a comprehensive and specialized curriculum-based system, develop evidence-based standardized nursing processes, and provide tailored training programs to address nurses' unique characteristics and individualized needs, thereby enhancing their proficiency in ST-related knowledge and skills. IMPACT: This study is the first to identify a poor level of ST knowledge among nurses nationwide, particularly in the four dimensions of risk assessment: prevention, treatment, classification, and observation. Based on the findings regarding demographic factors and ST experiences, an integrated management system and educational program should be implemented to improve nurses' awareness and knowledge in this field. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contributions.

6.
BMC Bioinformatics ; 24(1): 133, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37016291

RESUMO

BACKGROUND: RNA-seq followed by de novo transcriptome assembly has been a transformative technique in biological research of non-model organisms, but the computational processing of RNA-seq data entails many different software tools. The complexity of these de novo transcriptomics workflows therefore presents a major barrier for researchers to adopt best-practice methods and up-to-date versions of software. RESULTS: Here we present a streamlined and universal de novo transcriptome assembly and annotation pipeline, transXpress, implemented in Snakemake. transXpress supports two popular assembly programs, Trinity and rnaSPAdes, and allows parallel execution on heterogeneous cluster computing hardware. CONCLUSIONS: transXpress simplifies the use of best-practice methods and up-to-date software for de novo transcriptome assembly, and produces standardized output files that can be mined using SequenceServer to facilitate rapid discovery of new genes and proteins in non-model organisms.


Assuntos
Software , Transcriptoma , Análise de Sequência de RNA/métodos , RNA-Seq , Perfilação da Expressão Gênica , Anotação de Sequência Molecular
7.
Nat Chem Biol ; 17(10): 1037-1045, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34552220

RESUMO

As sessile organisms, plants evolved elaborate metabolic systems that produce a plethora of specialized metabolites as a means to survive challenging terrestrial environments. Decades of research have revealed the genetic and biochemical basis for a multitude of plant specialized metabolic pathways. Nevertheless, knowledge is still limited concerning the selective advantages provided by individual and collective specialized metabolites to the reproductive success of diverse host plants. Here we review the biological functions conferred by various classes of plant specialized metabolites in the context of the interaction of plants with their surrounding environment. To achieve optimal multifunctionality of diverse specialized metabolic processes, plants use various adaptive mechanisms at subcellular, cellular, tissue, organ and interspecies levels. Understanding these mechanisms and the evolutionary trajectories underlying their occurrence in nature will ultimately enable efficient bioengineering of desirable metabolic traits in chassis organisms.


Assuntos
Adaptação Fisiológica/genética , Evolução Biológica , Epigênese Genética/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , Plantas/metabolismo
8.
BMC Ophthalmol ; 23(1): 137, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37016343

RESUMO

OBJECTIVE: To compare post-treatment recurrence between ranibizumab injection and laser photocoagulation (LP) for type 1 retinopathy of prematurity (ROP), and explore the associated risk factors. METHODS: The clinical data of ROP infants treated with LP or ranibizumab in a NICU of China from October 2007 to November 2021 were retrospectively analyzed and compared, such as general condition, degree of ROP, therapeutic effectiveness and post-treatment recurrence. The dependent variable was recurrence after ROP treatment. Univariate and regression analysis of risk factors was performed. RESULTS: Of the 298 ROP infants (556 eyes), 58% of the eyes were treated with LP and the other 42% with ranibizumab. There was no significant difference in gestational age at birth, birth weight, sex, delivery mode, prenatal corticosteroids, ROP diagnosed before admission or after admission, and the duration of oxygen therapy between the two groups. However, the ratio of type 1 ROP and aggressive retinopathy of prematurity (A-ROP) in ranibizumab group was higher than that in LP group. The number of treatments, recurrence rate and recurrence interval in ranibizumab group were higher than those in LP group. However, there was no difference in the recurrence rate between the two groups after stratified analysis by the lesion area and the presence or absence of A-ROP. There was no significant difference in the final lesion regression between the two groups. Regression analysis showed that plus disease and ROP located in zone I were independent risk factors for post-treatment recurrence. CONCLUSION: There is no significant difference in the recurrence rate of ROP between ranibizumab injection and LP, and recurrence is mainly related to the severity of ROP. In half of our patients treated with A-ROP recurrences occur.


Assuntos
Ranibizumab , Retinopatia da Prematuridade , Recém-Nascido , Lactente , Humanos , Ranibizumab/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Retinopatia da Prematuridade/tratamento farmacológico , Retinopatia da Prematuridade/cirurgia , Estudos Retrospectivos , Injeções Intravítreas , Fotocoagulação a Laser , Idade Gestacional , Lasers , Resultado do Tratamento
9.
Proc Natl Acad Sci U S A ; 117(20): 10806-10817, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32371491

RESUMO

Radiation of the plant pyridoxal 5'-phosphate (PLP)-dependent aromatic l-amino acid decarboxylase (AAAD) family has yielded an array of paralogous enzymes exhibiting divergent substrate preferences and catalytic mechanisms. Plant AAADs catalyze either the decarboxylation or decarboxylation-dependent oxidative deamination of aromatic l-amino acids to produce aromatic monoamines or aromatic acetaldehydes, respectively. These compounds serve as key precursors for the biosynthesis of several important classes of plant natural products, including indole alkaloids, benzylisoquinoline alkaloids, hydroxycinnamic acid amides, phenylacetaldehyde-derived floral volatiles, and tyrosol derivatives. Here, we present the crystal structures of four functionally distinct plant AAAD paralogs. Through structural and functional analyses, we identify variable structural features of the substrate-binding pocket that underlie the divergent evolution of substrate selectivity toward indole, phenyl, or hydroxyphenyl amino acids in plant AAADs. Moreover, we describe two mechanistic classes of independently arising mutations in AAAD paralogs leading to the convergent evolution of the derived aldehyde synthase activity. Applying knowledge learned from this study, we successfully engineered a shortened benzylisoquinoline alkaloid pathway to produce (S)-norcoclaurine in yeast. This work highlights the pliability of the AAAD fold that allows change of substrate selectivity and access to alternative catalytic mechanisms with only a few mutations.


Assuntos
Descarboxilases de Aminoácido-L-Aromático/química , Domínio Catalítico , Evolução Molecular , Proteínas de Plantas/química , Aminoácidos Aromáticos/química , Aminoácidos Aromáticos/metabolismo , Descarboxilases de Aminoácido-L-Aromático/genética , Descarboxilases de Aminoácido-L-Aromático/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Especificidade por Substrato
10.
Australas J Dermatol ; 64(3): e224-e228, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37403826

RESUMO

Linear IgA/IgG bullous dermatosis (LAGBD) is a relatively rare autoimmune bullous disease characterized by both IgA and IgG antibodies to basement membrane zone. The heterogeneity and pathogenesis of antibodies and the relationship between IgA and IgG in LAGBD have not been fully elucidated. We observed clinical, histological and immunological features of three LAGBD cases at different time points in the disease course. In our cohort, two cases showed IgA antibodies to epidermal antigens vanished when their lesions cleared after 3 months of treatment. One refractory case showed increasing antigens targeted by IgA antibodies with the progression of the disease. Collectively, the results suggest that IgA antibodies may play a major role in LAGBD. In addition, epitope spreading may be related to disease relapse and treatment refractory.


Assuntos
Doenças Autoimunes , Dermatose Linear Bolhosa por IgA , Humanos , Dermatose Linear Bolhosa por IgA/diagnóstico , Dermatose Linear Bolhosa por IgA/tratamento farmacológico , Autoanticorpos , Doenças Autoimunes/diagnóstico , Imunoglobulina G , Imunoglobulina A
11.
J Asian Nat Prod Res ; 25(10): 976-982, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36946084

RESUMO

Two previously undescribed flavonoid thioglucosides lepidiumflavonosides A and B (1-2) and two known megastigmane compounds (7E,9S)-9-hydroxy-5,7-megastigmadien-4-one 9-O-ß-D-glucopyranoside (3) and (9S)-4-oxo-ß-inol ß-D-glucopyranoside (4) were isolated from the water extract of the seeds of Lepidium apetalum Willd. The structural elucidation of isolated compounds was unambiguously determined based on extensive 1D and 2D NMR spectroscopic analyses. All compounds were evaluated for their estrogen-like effects on MCF-7 cells in vitro. The results showed that compounds 1-4 significantly promoted the proliferation of MCF-7 cells, and the proliferation was antagonized by the specific ER antagonist ICI182,780, suggesting that compounds 1-4 might have the estrogen-like effect in vitro potentially.


Assuntos
Flavonoides , Lepidium , Flavonoides/farmacologia , Flavonoides/química , Tioglucosídeos/análise , Lepidium/química , Estrogênios/farmacologia , Sementes/química
12.
J Am Chem Soc ; 144(17): 7686-7692, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35438481

RESUMO

Moroidin is a bicyclic plant octapeptide with tryptophan side-chain cross-links, originally isolated as a pain-causing agent from the Australian stinging tree Dendrocnide moroides. Moroidin and its analog celogentin C, derived from Celosia argentea, are inhibitors of tubulin polymerization and, thus, lead structures for cancer therapy. However, low isolation yields from source plants and challenging organic synthesis hinder moroidin-based drug development. Here, we present biosynthesis as an alternative route to moroidin-type bicyclic peptides and report that they are ribosomally synthesized and posttranslationally modified peptides (RiPPs) derived from BURP-domain peptide cyclases in plants. By mining 793 plant transcriptomes for moroidin core peptide motifs within BURP-domain precursor peptides, we identified a moroidin cyclase in Japanese kerria, which catalyzes the installation of the tryptophan-indole-centered macrocyclic bonds of the moroidin bicyclic motif in the presence of cupric ions. Based on the kerria moroidin cyclase, we demonstrate the feasibility of producing diverse moroidins including celogentin C in transgenic tobacco plants and report specific cytotoxicity of celogentin C against a lung adenocarcinoma cancer cell line. Our study sets the stage for future biosynthetic development of moroidin-based therapeutics and highlights that mining plant transcriptomes can reveal bioactive cyclic peptides and their underlying cyclases from new source plants.


Assuntos
Peptídeos Cíclicos , Triptofano , Austrália , Peptídeos/metabolismo , Peptídeos/farmacologia , Peptídeos Cíclicos/química , Plantas , Processamento de Proteína Pós-Traducional , Triptofano/metabolismo
13.
Plant Cell ; 31(4): 848-861, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30886127

RESUMO

Pollen and microspore development are essential steps in the life cycle of all land plants that generate male gametes. Within flowering plants, pollen development occurs inside of the anther. Here, we report the identification of two class III peroxidase-encoding genes, PEROXIDASE9 (PRX9) and PRX40, that are genetically redundant and essential for proper anther and pollen development in Arabidopsis (Arabidopsis thaliana). Arabidopsis double mutants devoid of functional PRX9 and PRX40 are male sterile. The mutant anthers display swollen, hypertrophic tapetal cells and pollen grains, suggesting disrupted cell wall integrity. These phenotypes lead to nearly 100%-penetrant pollen degeneration upon anther maturation. Using immunochemical and biochemical approaches, we show that PRX9 and PRX40 likely cross-link extensins to contribute to tapetal cell wall integrity during anther development. This work suggests that PRX9 and PRX40 encode Arabidopsis extensin peroxidases and highlights the importance of extensin cross-linking during pollen development.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Plantas Geneticamente Modificadas/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Parede Celular/genética , Parede Celular/metabolismo , Parede Celular/fisiologia , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/fisiologia
14.
J Asian Nat Prod Res ; : 1-7, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35611800

RESUMO

Two new cyclotrypyamine alkaloids equisetinines A and B, as well as three known alkaloids (3-5) were isolated from the stems of Ephedra equisetina Bunge. Their structures were characterized by spectroscopic methods, and the absolute configurations of the new compounds were determined by interpretation of their electronic circular dichroism. Anti-asthmatic activities of compounds were evaluated by releasing ß-Hex in C48/80-induced RBL-2H3 cells, and compound 5 exhibited significant anti-asthmatic activities.

15.
Nat Prod Rep ; 38(1): 130-239, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32935693

RESUMO

Covering: up to June 2020Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are a large group of natural products. A community-driven review in 2013 described the emerging commonalities in the biosynthesis of RiPPs and the opportunities they offered for bioengineering and genome mining. Since then, the field has seen tremendous advances in understanding of the mechanisms by which nature assembles these compounds, in engineering their biosynthetic machinery for a wide range of applications, and in the discovery of entirely new RiPP families using bioinformatic tools developed specifically for this compound class. The First International Conference on RiPPs was held in 2019, and the meeting participants assembled the current review describing new developments since 2013. The review discusses the new classes of RiPPs that have been discovered, the advances in our understanding of the installation of both primary and secondary post-translational modifications, and the mechanisms by which the enzymes recognize the leader peptides in their substrates. In addition, genome mining tools used for RiPP discovery are discussed as well as various strategies for RiPP engineering. An outlook section presents directions for future research.


Assuntos
Biologia Computacional/métodos , Enzimas/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Engenharia de Proteínas/métodos , Produtos Biológicos/química , Produtos Biológicos/classificação , Produtos Biológicos/metabolismo , Enzimas/química , Hidroxilação , Metilação , Peptídeos/classificação , Peptídeos/genética , Fosforilação , Processamento de Proteína Pós-Traducional , Sinais Direcionadores de Proteínas/fisiologia , Ribossomos/metabolismo
16.
Nature ; 584(7819): 49-50, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32699367
17.
Proc Natl Acad Sci U S A ; 115(46): E10961-E10969, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30373830

RESUMO

The plant kingdom contains vastly untapped natural product chemistry, which has been traditionally explored through the activity-guided approach. Here, we describe a gene-guided approach to discover and engineer a class of plant ribosomal peptides, the branched cyclic lyciumins. Initially isolated from the Chinese wolfberry Lycium barbarum, lyciumins are protease-inhibiting peptides featuring an N-terminal pyroglutamate and a macrocyclic bond between a tryptophan-indole nitrogen and a glycine α-carbon. We report the identification of a lyciumin precursor gene from L. barbarum, which encodes a BURP domain and repetitive lyciumin precursor peptide motifs. Genome mining enabled by this initial finding revealed rich lyciumin genotypes and chemotypes widespread in flowering plants. We establish a biosynthetic framework of lyciumins and demonstrate the feasibility of producing diverse natural and unnatural lyciumins in transgenic tobacco. With rapidly expanding plant genome resources, our approach will complement bioactivity-guided approaches to unlock and engineer hidden plant peptide chemistry for pharmaceutical and agrochemical applications.


Assuntos
Perfilação da Expressão Gênica/métodos , Genes de Plantas , Peptídeos Cíclicos/genética , Plantas/genética , Sequência de Aminoácidos/genética , Produtos Biológicos/química , Genoma , Genômica/métodos , Lignanas/biossíntese , Peptídeos/química , Peptídeos/genética , Peptídeos Cíclicos/metabolismo , Processamento de Proteína Pós-Traducional , Ribossomos/genética , Ribossomos/metabolismo
18.
Proc Natl Acad Sci U S A ; 115(22): E5223-E5232, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29760092

RESUMO

Xanthohumol (XN) and demethylxanthohumol (DMX) are specialized prenylated chalconoids with multiple pharmaceutical applications that accumulate to high levels in the glandular trichomes of hops (Humulus lupulus L.). Although all structural enzymes in the XN pathway have been functionally identified, biochemical mechanisms underlying highly efficient production of XN have not been fully resolved. In this study, we characterized two noncatalytic chalcone isomerase (CHI)-like proteins (designated as HlCHIL1 and HlCHIL2) using engineered yeast harboring all genes required for DMX production. HlCHIL2 increased DMX production by 2.3-fold, whereas HlCHIL1 significantly decreased DMX production by 30%. We show that CHIL2 is part of an active DMX biosynthetic metabolon in hop glandular trichomes that encompasses a chalcone synthase (CHS) and a membrane-bound prenyltransferase, and that type IV CHI-fold proteins of representative land plants contain conserved function to bind with CHS and enhance its activity. Binding assays and structural docking uncover a function of HlCHIL1 to bind DMX and naringenin chalcone to stabilize the ring-open configuration of these chalconoids. This study reveals the role of two HlCHILs in DMX biosynthesis in hops, and provides insight into their evolutionary development from the ancestral fatty acid-binding CHI-fold proteins to specialized auxiliary proteins supporting flavonoid biosynthesis in plants.


Assuntos
Flavonoides/biossíntese , Humulus/enzimologia , Liases Intramoleculares , Proteínas de Plantas , Prenilação/genética , Aciltransferases/química , Aciltransferases/metabolismo , Flores/metabolismo , Humulus/genética , Liases Intramoleculares/química , Liases Intramoleculares/genética , Liases Intramoleculares/metabolismo , Redes e Vias Metabólicas/genética , Mutação/genética , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Análise de Sequência de DNA
19.
J Biol Chem ; 294(42): 15193-15205, 2019 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-31481469

RESUMO

As a means to maintain their sessile lifestyle amid challenging environments, plants produce an enormous diversity of compounds as chemical defenses against biotic and abiotic insults. The underpinning metabolic pathways that support the biosynthesis of these specialized chemicals in divergent plant species provide a rich arena for understanding the molecular evolution of complex metabolic traits. Rosmarinic acid (RA) is a phenolic natural product first discovered in plants of the mint family (Lamiaceae) and is recognized for its wide range of medicinal properties and potential applications in human dietary and medical interventions. Interestingly, the RA chemotype is present sporadically in multiple taxa of flowering plants as well as some hornworts and ferns, prompting the question whether its biosynthesis arose independently across different lineages. Here we report the elucidation of the RA biosynthetic pathway in Phacelia campanularia (desert bells). This species represents the borage family (Boraginaceae), an RA-producing family closely related to the Lamiaceae within the Lamiids clade. Using a multi-omics approach in combination with functional characterization of candidate genes both in vitro and in vivo, we found that RA biosynthesis in P. campanularia involves specific activities of a BAHD acyltransferase and two cytochrome P450 hydroxylases. Further phylogenetic and comparative structure-function analyses of the P. campanularia RA biosynthetic enzymes clearly indicate that RA biosynthesis has evolved independently at least twice in the Lamiids, an exemplary case of chemotypic convergence through disparate evolutionary trajectories.


Assuntos
Cinamatos/metabolismo , Depsídeos/metabolismo , Evolução Molecular , Lamiaceae/metabolismo , Aciltransferases/genética , Aciltransferases/metabolismo , Vias Biossintéticas , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Lamiaceae/classificação , Lamiaceae/genética , Redes e Vias Metabólicas , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Rosmarínico
20.
Plant Cell ; 29(8): 1907-1926, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28733420

RESUMO

Lignification of cell wall appositions is a conserved basal defense mechanism in the plant innate immune response. However, the genetic pathway controlling defense-induced lignification remains unknown. Here, we demonstrate the Arabidopsis thaliana SG2-type R2R3-MYB transcription factor MYB15 as a regulator of defense-induced lignification and basal immunity. Loss of MYB15 reduces the content but not the composition of defense-induced lignin, whereas constitutive expression of MYB15 increases lignin content independently of immune activation. Comparative transcriptional and metabolomics analyses implicate MYB15 as necessary for the defense-induced synthesis of guaiacyl lignin and the basal synthesis of the coumarin metabolite scopoletin. MYB15 directly binds to the secondary wall MYB-responsive element consensus sequence, which encompasses the AC elements, to drive lignification. The myb15 and lignin biosynthetic mutants show increased susceptibility to the bacterial pathogen Pseudomonas syringae, consistent with defense-induced lignin having a major role in basal immunity. A scopoletin biosynthetic mutant also shows increased susceptibility independently of immune activation, consistent with a role in preformed defense. Our results support a role for phenylalanine-derived small molecules in preformed and inducible Arabidopsis defense, a role previously dominated by tryptophan-derived small molecules. Understanding the regulatory network linking lignin biosynthesis to plant growth and defense will help lignin engineering efforts to improve the production of biofuels and aromatic industrial products as well as increase disease resistance in energy and agricultural crops.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/imunologia , Arabidopsis/metabolismo , Lignina/metabolismo , Imunidade Vegetal , Fatores de Transcrição/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Flagelina/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Lignina/biossíntese , Fenóis/metabolismo , Regiões Promotoras Genéticas/genética , Ligação Proteica , Pseudomonas syringae/fisiologia , Escopoletina/farmacologia , Homologia de Sequência de Aminoácidos , Solubilidade , Fatores de Transcrição/genética
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