Review
Biochemistry & Molecular Biology
Michal K. Jastrzebski, Agnieszka A. Kaczor, Tomasz M. Wrobel
Summary: This review highlights the importance of lysergic acid as a representative of ergot alkaloids, discussing various methods of total synthesis of lysergic acid and the topic of biosynthesis.
Article
Chemistry, Multidisciplinary
Yinan Wu, Chang Liu, Anna Koganitsky, Franklin L. Gong, Sijin Li
Summary: Discovering natural product biosynthetic pathways of medicinal plants is challenging. In this study, a yeast-based screening method was developed to capture the protein-protein interactions (PPI) between plant enzymes. Combining this method with plant multiomics analysis, four enzyme complexes and their organized pathways were discovered from kratom. This study highlights the opportunity of leveraging post-translational regulation features to discover novel plant natural product biosynthetic pathways.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemical Research Methods
Nan Wu, Mingdong Yao, Wenhai Xiao, Tianyu Dong, Haidi Ma, Yingjin Yuan, Xianli Du, Ying Wang
Summary: The current study proposes a modular compartmentalization strategy for identifying and modifying the bottleneck step in agroclavine overproduction. The agroclavine synthetic pathway was reconstituted in yeast to enhance pathway efficiency and improve agroclavine yield.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Chunyan An, Fangfang Zhu, Yongpeng Yao, Kexin Zhang, Wei Wang, Jun Zhang, Guangzheng Wei, Yue Xia, Qiang Gao, Shu-Shan Gao
Summary: Ergot alkaloids are important bioactive natural products. The dioxygenase Aj_EasH from Aspergillus japonicus has been found to catalyze both the formation of the cyclopropyl ring in cycloclavine and the asymmetric hydroxylation of other ergot alkaloids. Molecular docking studies revealed the substrate binding and catalytic mechanism, suggesting the potential of Aj_EasH for producing diverse and bioactive ergot alkaloid derivatives.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Biology
Wesley T. Beaulieu, Daniel G. Panaccione, Quynh N. Quach, Katy L. Smoot, Keith Clay
Summary: Beaulieu et al. report on the distribution of bioactive ergot alkaloids produced by symbiotic fungi found primarily in four clades of morning glories. Their results identify the repeated evolution of this symbiosis in Convolvulaceae, and a correlation between ergot alkaloid presence and greater seed mass that is consistent with a defensive function.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Alexander O. Brachmann, Silke I. Probst, Joel Ruethi, Darya Dudko, Helge B. Bode, Joern Piel
Summary: This study identified a cryptic biosynthetic locus encoding an N-acyltransferase and a non-heme diiron desaturase-like enzyme in a bacterium producing labradorin through transposon mutagenesis. Heterologous expression in E. coli demonstrated the ability of both enzymes to produce indolyloxazoles, and stable-isotope feeding experiments provided evidence for an unusual desaturase mechanism generating the oxazole by decarboxylative cyclization.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Biochemistry & Molecular Biology
Erika Plazas, Nicoletta Faraone
Summary: Neuropsychiatric diseases such as depression, anxiety, and post-traumatic stress pose a significant challenge to global health systems due to their increasing prevalence, uncertain neuropathology, and lack of effective pharmacological treatments. The use of indole alkaloids derived from magic mushrooms has shown promising potential as an alternative to synthetic drugs for the treatment of these disorders. This review highlights the physicochemical and pharmacological characteristics of indole alkaloids, particularly those derived from magic mushrooms, and their potential as safe and effective therapeutic agents.
Article
Biology
Kelcie N. Britton, Chey R. Steen, Kyle A. Davis, Jessi K. Sampson, Daniel G. Panaccione
Summary: In this study, a gene named easP in the fungus Metarhizium brunneum was found to contribute to the accumulation of lysergic acid alpha-hydroxyethylamide (LAH) but is not essential. Another gene estA in the same pathway was found to have no role in LAH synthesis.
BMC RESEARCH NOTES
(2022)
Review
Pharmacology & Pharmacy
Qinfang Zheng, Ye Wang, Shuihan Zhang
Summary: This work reviews the progress in the phytochemical and biological investigations of bioactive components from Lobelia species, highlighting the shift in research focus towards novel chemical classes and molecular mechanisms of these components.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Organic
Francesca Bartoccini, Alessio Regni, Michele Retini, Giovanni Piersanti
Summary: A unified enantioselective synthesis and biological evaluation of all rugulovasine stereoisomers were reported. A divergent approach was used to synthesize the unsaturated oxaspirolactone moiety, allowing rapid synthesis of all stereoisomers. These compounds showed preferred selectivity for the serotonin 1 A receptor.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Plant Sciences
Tao Tao, Ping Zhang, Zhi Zeng, Min Wang
Summary: Natural products have a critical role in drug development, especially in cancer therapy. There is increasing evidence that many natural products may modulate autophagy in cervical cancer. Understanding the mechanisms of these natural products helps to develop medications for cervical cancer treatments.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Laura Carbonell-Rozas, Arianna Alabrese, Raffaele Meloni, Laura Righetti, Massimo Blandino, Chiara Dall'Asta
Summary: Ergot alkaloids (EAs) were found to be widely present in major and minor cereals in the Mediterranean growing areas, especially under favorable weather conditions. The contamination of EAs was influenced by the harvest year, with 2020 showing the highest levels of contamination. There was a significant co-occurrence of EAs in the cereal samples, with 60% of the samples being contaminated. Rye was the most susceptible crop to fungal infection, while the accumulation of EAs in tritordeum and emmer was reported for the first time.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Alistair T. Richardson, Rosannah C. Cameron, Luke J. Stevenson, A. Jonathan Singh, Yonathan Lukito, Daniel Berry, Matthew J. Nicholson, Emily J. Parker
Summary: Nodulisporic acids (NAs) are potent anti-insect compounds with complex biosynthetic pathways. This study revealed a highly complex biosynthetic network that produces multiple end products through the expression of specific genes. One pivotal enzyme, NodJ, was found to be responsible for the production of multiple metabolites, resulting in the formation of a complex metabolic grid.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Jeff K. Kerkovius, Andrea Stegner, Aneta Turlik, Pik Hoi Lam, Kendall N. Houk, Sarah E. Reisman
Summary: (+)-Matrine and (+)-isomatrine, tetracyclic alkaloids derived from Sophora flavescens, are synthesized through a biosynthetic pathway involving (-)-lysine and the intermediacy of Delta 1-piperidine. A new dearomative annulation reaction using pyridine as a stable surrogate for Delta 1-piperidine allows for the efficient synthesis of matrine alkaloids. Isomatrine, synthesized in four steps from inexpensive commercially available chemicals, serves as the precursor to other lupin alkaloids.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Polymer Science
Huan An, Xuehui Deng, Fang Wang, Pingcui Xu, Nani Wang
Summary: Natural products have shown their therapeutic value in treating various diseases, but their low solubility and poor bioavailability present challenges. To overcome these issues, drug nanocarriers, particularly dendrimers, have been developed. This review summarizes the structures of dendrimer-based nanocarriers and their applications in alkaloids and polyphenols, while also discussing future challenges and perspectives in clinical therapy.
Article
Plant Sciences
Konstantinos Koudounas, Gregory Guirimand, Luisa Fernanda Rojas Hoyos, Ines Carqueijeiro, Pamela Lemos Cruz, Emily Stander, Natalja Kulagina, Jennifer Perrin, Audrey Oudin, Sebastien Besseau, Arnaud Lanoue, Lucia Atehortua, Benoit St-Pierre, Nathalie Giglioli-Guivarc'h, Nicolas Papon, Sarah E. O'Connor, Vincent Courdavault
Summary: Many plant species from the Apocynaceae, Loganiaceae and Rubiaceae families produce a variety of monoterpene indole alkaloids (MIAs) which have pharmacological properties. The subcellular localization of N-methyltransferases (NMTs) in MIA-producing plants adds a new layer of complexity to the biosynthetic pathway.
PLANT AND CELL PHYSIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Chloe Langley, Evangelos Tatsis, Benke Hong, Yoko Nakamura, Christian Paetz, Clare E. M. Stevenson, Jerome Basquin, David M. Lawson, Lorenzo Caputi, Sarah E. O'Connor
Summary: This study reports the crystal structure of the plant enzyme DPAS, which catalyzes the non-canonical 1,4-reduction of an alpha,beta-unsaturated iminium moiety. The comparison with classical aldehyde reducing enzymes reveals that this reaction does not require proton relay or the presence of a catalytic zinc ion.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Genetics & Heredity
Emily Amor Stander, Clement Cuello, Caroline Birer-Williams, Natalja Kulagina, Hans Jansen, Ines Carqueijeiro, Louis-Valentin Meteignier, Valentin Verges, Audrey Oudin, Nicolas Papon, Ron Dirks, Michael Krogh Jensen, Sarah Ellen O'Connor, Thomas Duge de Bernonville, Sebastien Besseau, Vincent Courdavault
Summary: In this study, the genome of Vinca minor was sequenced and analyzed to identify genes related to monoterpene indole alkaloids. A functionally validated gene was discovered with the potential for large-scale production of these bioactive compounds in heterologous expression systems.
G3-GENES GENOMES GENETICS
(2022)
Article
Biology
Quentin M. Dudley, Seohyun Jo, Delia Ayled Serna Guerrero, Monika Chhetry, Mark A. Smedley, Wendy A. Harwood, Nathaniel H. Sherden, Sarah E. O'Connor, Lorenzo Caputi, Nicola J. Patron
Summary: In this study, the pathway for strictosidine, a key intermediate of all MIAs, was successfully reconstituted in Nicotiana benthamiana. The use of transcriptomic analysis led to the identification of upregulated glycosyltransferases, which were targeted for mutation in plant lines. The expression of the early MIA pathway in these lines resulted in a more favorable product profile. The production of strictosidine in planta expands the range of MIA products amenable to biological synthesis.
COMMUNICATIONS BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Philipp Stephan, Chloe Langley, Daniela Winkler, Jerome Basquin, Lorenzo Caputi, Sarah E. E. O'Connor, Hajo Kries
Summary: Engineering of biosynthetic enzymes is used to synthesize antibiotics analogues. This study focuses on nonribosomal peptide synthetases (NRPSs) responsible for producing antimicrobial peptides. By directed evolution, the substrate specificity of an adenylation domain of a Pro-specific NRPS module was completely switched to a non-standard amino acid. This achievement was made through screening of mutant libraries and can be replicated with different substrates and NRPS modules. New possibilities for modifying NRPS specificity in a biosynthetically useful way are presented.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Plant Sciences
Larissa C. Laforest, Michelle A. Kuntz, Siva Rama Raju Kanumuri, Sushobhan Mukhopadhyay, Abhisheak Sharma, Sarah E. O'Connor, Christopher R. McCurdy, Satya Swathi Nadakuduti
Summary: This study quantified 10 alkaloids in different tissues and cultivars of M. speciosa, revealing that mitragynine accumulated the highest in leaves and was absent in roots. Juvenile leaves also accumulated higher levels of corynantheidine and speciociliatine. Different cultivars of M. speciosa had altered alkaloidal profiles and gene expression, suggesting the impact of hybridization events.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Multidisciplinary
Carsten Schotte, Yindi Jiang, Dagny Grzech, Thu-Thuy T. Dang, Larissa C. Laforest, Francisco Leon, Marco Mottinelli, Satya Swathi Nadakuduti, Christopher R. McCurdy, Sarah E. O'Connor
Summary: The central biosynthetic steps responsible for the formation of mitragynine and related alkaloids in Mitragyna speciosa (kratom) have been identified, shedding light on the mechanistic basis and enabling the enzymatic production of these compounds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Chenxin Li, Joshua C. Wood, Anh Hai Vu, John P. Hamilton, Carlos Eduardo Rodriguez Lopez, Richard M. E. Payne, Delia Ayled Serna Guerrero, Klaus Gase, Kotaro Yamamoto, Brieanne Vaillancourt, Lorenzo Caputi, Sarah E. O'Connor, C. Robin Buell
Summary: Through genomic and single-cell analysis, we investigated the biosynthetic pathway of monoterpene indole alkaloids in Catharanthus roseus. We identified gene clusters and gene duplications involved in the pathway, as well as a transporter. Single-cell transcriptomics and metabolomics revealed cell-type-specific expression patterns and the identification of a reductase product. The study also uncovered cell-type-specific expression in the root pathway.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Marcus Daniel Brandbjerg Bohn Lorensen, Nanna Bjarnholt, Benoit St-Pierre, Sarah Heinicke, Vincent Courdavault, Sarah O'Connor, Christian Janfelt
Summary: This study used mass spectrometry imaging (MSI) techniques to explore the biosynthetic pathway of monoterpene indole alkaloids (MIAs). The results showed that ions corresponding to intermediates of reserpine were localized in different tissues of Rauvolfia tetraphylla. By feeding stable-isotope labeled precursors, it was confirmed that these intermediates were synthesized in planta. In addition, a potential novel dimeric MIA was discovered in leaf tissue of R. tetraphylla.
Article
Biochemistry & Molecular Biology
Eike Schafer, Paula S. Seibold, Stefan Bartram, Felix Trottmann, Veit G. Haensch, Markus Gressler, Andrew R. Chadeayne, Christian Hertweck, Sarah E. O'Connor, Dirk Hoffmeister
Summary: This study identified several compounds present in various Psilocybe species, including cubebol, β-copaene, δ-cadinene, and germacrene D, through fluorescence staining and transgenic techniques. The results also revealed the presence of related enzymes encoded by CubA in multiple Psilocybe species.
Article
Multidisciplinary Sciences
Prashant D. Sonawane, Sachin A. Gharat, Adam Jozwiak, Ranjit Barbole, Sarah Heinicke, Efrat Almekias-Siegl, Sagit Meir, Ilana Rogachev, Sarah E. O'Connor, Ashok P. Giri, Asaph Aharoni
Summary: During tomato fruit ripening, bitter and toxic steroidal glycoalkaloids (SGAs) are converted to nonbitter and less toxic forms, but the enzyme responsible for acylation remains unknown. The authors discovered a BAHD-type acyltransferase that catalyzes the acylation step in the biosynthesis of non-bitter SGAs in tomatoes. This finding provides insight into the metabolism of SGAs in ripe tomatoes and sheds light on the evolution and breeding of sweet-tasting tomato varieties.
NATURE COMMUNICATIONS
(2023)
Article
Plant Sciences
Lovely Mae F. Lawas, Mohamed O. Kamileen, C. Robin Buell, Sarah E. O'Connor, Courtney P. Leisner
Summary: Blueberries are known for their nutritional quality and have been found to produce iridoids, which have health-promoting benefits. However, the genes involved in the biosynthesis of iridoids and their production in blueberries have not yet been fully understood.
Article
Plant Sciences
Maritta Kunert, Chloe Langley, Rosalind Lucier, Kerstin Ploss, Carlos E. Rodriguez Lopez, Delia A. Serna Guerrero, Eva Rothe, Sarah E. O'Connor, Prashant D. Sonawane
Summary: Cardenolides, such as digoxin, have been used to treat congenital heart failure, cancer, and other chronic diseases. This study identifies CYP87A enzymes that catalyze the formation of pregnenolone, the key entry point to the cardenolide pathway in plants.
Article
Plant Sciences
Caiqiong Yang, Rayko Halitschke, Sarah E. O'Connor
Summary: Triterpenes are bioactive compounds that play a crucial role in plant defense against biotic stressors. This study identified two oxidosqualene cyclases in tobacco that are involved in triterpene biosynthesis and demonstrated their importance in defense against insect larvae.
