Angew Chem Int Ed Engl , IF:15.336 , 2021 Jul , V60 (29) : P15963-15971 doi: 10.1002/anie.202102831
Bioinspired Network Analysis Enabled Divergent Syntheses and Structure Revision of Pentacyclic Cytochalasans.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, 132 Lanhei Road, Kunming, 650201, China.; University of Chinese Academy of Sciences, Beijing, 100049, China.; State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China.
We accomplished the divergent total syntheses of ten pentacyclic cytochalasans (aspergillin PZ, trichodermone, trichoderones, flavipesines, and flavichalasines) from a common precursor aspochalasin D and revised the structures of trichoderone B, spicochalasin A, flavichalasine C, aspergilluchalasin based on structure network analysis of the cytochalasans biosynthetic pathways and DFT calculations. The key steps of the syntheses include transannular alkene/epoxyalkene and carbonyl-ene cyclizations to establish the C/D ring of pentacyclic aspochalasans. Our bioinspired approach to these pentacyclic cytochalasans validate the proposed biosynthetic speculation from a chemical view and provide a platform for the synthesis of more than 400 valuable cytochalasans bearing different macrocycles and amino-acid residues.
PMID: 33860618
Brief Bioinform , IF:11.622 , 2021 Jul , V22 (4) doi: 10.1093/bib/bbaa244
Multimodal analysis of gene expression from postmortem brains and blood identifies synaptic vesicle trafficking genes to be associated with Parkinson's disease.
Department of Neurology, Zhujiang Hospital, Southern Medical University, China.; Department of Neurology, Zhujiang Hospital of Southern Medical University, China.; Genetics, Genomics, and Bioinformatics Program, Department of Botany and Plant Sciences of University of California, USA.; Department of Neurology of Zhujiang Hospital of Southern Medical University, China.; Clinical Research Centre of Zhujiang Hospital of Southern Medical University, China.; Department of Neurology of First Municipal Hospital of Guangzhou, China.; Laboratory for Neuromodulation of Guangdong Second Provincial General Hospital, China.; Department of Neurology of Fifth Affiliated Hospital of Southern Medical University, China.; Department of Neurology, Zhujiang Hospital of Southern Medical University, Guanghzou, China.; Department of Neurology of National Neuroscience Institute, Singapore General Hospital, Duke-NUS Medical School.; University of California, San Francisco, USA.; Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.; International Parkinson Foundation Centre of Excellence at Kings College Hospital and research director at Kings College Hospital, and Kings College, Denmark Hill, London, SE5 9RS UK.; Department of Pathology, University of Washington School of Medicine (USA).; Department of Neurology, National Neuroscience Institute, Singapore General Hospital, and a professor in the Duke-NUS Medical School, Singapore.; Head of Department of Neurology, Zhujiang Hospital, Southern Medical University, China.
OBJECTIVE: We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson's disease (PD) patients and healthy controls (HC). METHODS: We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein-protein interaction (PPI) networks. Next, we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson's Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis (MLRA) and receiver operating characteristic (ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. RESULTS: We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P < 0.05), and PPI analysis revealed that SVT genes PPP2CA, SYNJ1, NSF and PPP3CB were the top four hub node genes in MEturquoise (P < 0.001). The levels of these four genes in PD postmortem brains were lower than those in HC brains. We found lower blood levels of PPP2CA, SYNJ1 and NSF in PD compared with HC, and lower SYNJ1 in PD compared with PPS (P < 0.05). SYNJ1, negatively correlated to PD severity, displayed an excellent power to discriminating PD from HC and PPS. CONCLUSIONS: This study highlights that SVT genes, especially SYNJ1, may be promising markers in discriminating PD from HCs and PPS.
PMID: 33079984
New Phytol , IF:10.151 , 2021 Jul doi: 10.1111/nph.17618
Integrative analyses of metabolome and genome-wide transcriptome reveal the regulatory network governing flavor formation in kiwifruit (Actinidia chinensis).
Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610065, Sichuan, P.R. China.; College of Agriculture & Biotechnology, Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zhejiang University, Zijingang Campus, Hangzhou, 310058, China.; Key Laboratory of Breeding and Utilization of Kiwifruit in Sichuan Province, Sichuan Provincial Academy of Natural Resource Sciences, Chengdu, 610015, China.; Key Laboratory of Plant Hormones and Development Regulation of Chongqing, School of Life Sciences, Chongqing University, Chongqing, 405200, China.; School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, United Kingdom.; GBF Laboratory, Universite de Toulouse, INRA, Castanet-Tolosan, 31320, France.
Soluble sugars, organic acids and volatiles are important components that determine unique fruit flavor and consumer preferences. However, the metabolic dynamics and underlying regulatory networks that modulate overall flavor formation during fruit development and ripening remain largely unknown for most fruit species. In this study, by integrating flavor-associated metabolism and transcriptome data from 12 fruit developmental and ripening stages of Actinidia chinensis cv. Hongyang, we generated a global map of changes in the flavor-related metabolites throughout development and ripening of kiwifruit. Using this dataset, we constructed complex regulatory networks allowing to identify key structural genes and transcription factors that regulate the metabolism of soluble sugars, organic acids and important volatiles in kiwifruit. Moreover, our study revealed the regulatory mechanism involving key transcription factors regulating flavor metabolism. The modulation of flavor metabolism by the identified key transcription factors was confirmed in different kiwifruit species providing the proof of concept that our dataset provides a suitable tool for clarification of the regulatory factors controlling flavor biosynthetic pathways that have not been previously illuminated. Overall, in addition to providing new insight into the metabolic regulation of flavor during fruit development and ripening, the outcome of our study establishes a foundation for flavor improvement in kiwifruit.
PMID: 34255862
Appl Microbiol Biotechnol , IF:4.813 , 2021 Jul doi: 10.1007/s00253-021-11431-7
The impact of bZIP Atf1ortholog global regulators in fungi.
Department of Molecular Biotechnology and Microbiology, Institute of Biotechnology, University of Debrecen, P.O. Box 63, Debrecen, H-4010, Hungary. leiter.eva@science.unideb.hu.; Department of Molecular Biotechnology and Microbiology, Institute of Biotechnology, University of Debrecen, P.O. Box 63, Debrecen, H-4010, Hungary.; Hungarian University of Agriculture and Life Sciences, Godollo, Hungary.
Regulation of signal transduction pathways is crucial for the maintenance of cellular homeostasis and organismal development in fungi. Transcription factors are key elements of this regulatory network. The basic-region leucine zipper (bZIP) domain of the bZIP-type transcription factors is responsible for DNA binding while their leucine zipper structural motifs are suitable for dimerization with each other facilitiating the formation of homodimeric or heterodimeric bZIP proteins. This review highlights recent knowledge on the function of fungal orthologs of the Schizosaccharomyces pombe Atf1, Aspergillus nidulans AtfA, and Fusarium verticillioides FvAtfA, bZIP-type transcription factors with a special focus on pathogenic species. We demonstrate that fungal Atf1-AtfA-FvAtfA orthologs play an important role in vegetative growth, sexual and asexual development, stress response, secondary metabolite production, and virulence both in human pathogens, including Aspergillus fumigatus, Mucor circinelloides, Penicillium marneffei, and Cryptococcus neoformans and plant pathogens, like Fusarium ssp., Magnaporthe oryzae, Claviceps purpurea, Botrytis cinerea, and Verticillium dahliae. KEY POINTS: * Atf1 orthologs play crucial role in the growth and development of fungi. * Atf1 orthologs orchestrate environmental stress response of fungi. * Secondary metabolite production and virulence are coordinated by Atf1 orthologs.
PMID: 34302199
Tree Physiol , IF:4.196 , 2021 Jul , V41 (7) : P1247-1263 doi: 10.1093/treephys/tpaa180
UV-B-induced molecular mechanisms of stress physiology responses in the major northern Chinese conifer Pinus tabuliformis Carr.
Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, National Engineering Laboratory for Tree Breeding, Key Laboratory of Genetics and Breeding in Forest Trees and Ornamental Plants, Ministry of Education, College of Biological Sciences and Technology, Beijing Forestry University, 35 Qinghua E Rd, Beijing 100083, China.; Department of Ecology and Environmental Science, Umea Plant Science Centre, Umea University, SE-901 87 Umea, Sweden.; Qigou State-owned Forest Farm, Qigou Village, Qigou Town, Pingquan County, Chengde City, Hebei Province, 067509, China.; Department of Forest and Conservation Sciences, The University of British Columbia, 2424 Main Mall, Vancouver, British Columbia V6T 1Z4 Canada.; Department des Sciences du Bois et de la Foret, Faculte de Foresterie, de Geographie et Geomatique, Universite Laval Quebec, 1030 Avenue de la Medecine, Quebec, QC G1V 0A6, Canada.
During their lifetimes, plants are exposed to different abiotic stress factors eliciting various physiological responses and triggering important defense processes. For UV-B radiation responses in forest trees, the genetics and molecular regulation remain to be elucidated. Here, we exposed Pinus tabuliformis Carr., a major conifer from northern China, to short-term high-intensity UV-B and employed a systems biology approach to characterize the early physiological processes and the hierarchical gene regulation, which revealed a temporal transition from primary to secondary metabolism, the buildup of enhanced antioxidant capacity and stress-signaling activation. Our findings showed that photosynthesis and biosynthesis of photosynthetic pigments were inhibited, while flavonoids and their related derivates biosynthesis, as well as glutathione and glutathione S-transferase mediated antioxidant processes, were enhanced. Likewise, stress-related phytohormones (jasmonic acid, salicylic acid and ethylene), kinase and reactive oxygen species signal transduction pathways were activated. Biological processes regulated by auxin and karrikin were, for the first time, found to be involved in plant defense against UV-B by promoting the biosynthesis of flavonoids and the improvement of antioxidant capacity in our research system. Our work evaluated the physiological and transcriptome perturbations in a conifer's response to UV-B, and generally, highlighted the necessity of a systems biology approach in addressing plant stress biology.
PMID: 33416074