Article
Biochemistry & Molecular Biology
Tim Schaefer, Kristina Kramer, Sebastiaan Werten, Bernhard Rupp, Dirk Hoffmeister
Summary: This study characterized the in vitro biochemical properties of Psilocybe cubensis PsiD and performed in silico modeling of its structure. The experimental results confirmed the autocatalytic cleavage of the pro-protein by a non-canonical serine protease triad.
Review
Chemistry, Multidisciplinary
Claudius Lenz, Alexander Sherwood, Robert Kargbo, Dirk Hoffmeister
Summary: Psilocybe fungi, commonly known as magic mushrooms, are famous for their major natural product psilocybin derived from l-tryptophan, but recent research has shown a more diverse secondary metabolism originating from this amino acid. This minireview highlights l-tryptophan and various Psilocybe natural products, including psilocybin, blue-colored psilocyl oligomers, beta-carbolines, and N,N-dimethyl-l-tryptophan, with insights into their biosynthesis.
Article
Biotechnology & Applied Microbiology
Jessica E. Flower, William J. J. Gibbons Jr, Alexandra M. Adams, Xin Wang, Caroline N. Broude, J. Andrew Jones
Summary: Traditional psychedelics are being developed as potential alternative drugs for treating mental illness, and sustainable production methods are needed to support further research. This study expanded upon current bacterial psilocybin biosynthesis by introducing a new enzyme, PsiH, which enabled the production of psilocybin and 13 derivatives. The study also explored the potential of using various indole derivatives to produce previously unstudied drug candidates.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
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
Biochemistry & Molecular Biology
Parbir S. Grewal, Jennifer A. Samson, Jordan J. Baker, Brian Choi, John E. Dueber
Summary: This study demonstrates that by targeting the toxic enzyme NCS to the peroxisome and enlarging peroxisomes through the expression of engineered transcription factors, the production of (S)-reticuline and other alkaloids can be increased efficiently.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Pedram Mehrabi, Sihyun Sung, David von Stetten, Andreas Prester, Caitlin E. Hatton, Stephan Kleine-Doepke, Alexander Berkes, Gargi Gore, Jan-Philipp Leimkohl, Hendrik Schikora, Martin Kollewe, Holger Rohde, Matthias Wilmanns, Friedjof Tellkamp, Eike C. Schulz
Summary: The authors introduce the spitrobot, a crystal plunger, enabling cryo-trapping with millisecond time-resolution via the liquid application method (LAMA). Ligand binding and reaction intermediates are demonstrated in three different enzymes. We also trap reaction intermediates and conformational changes in macroscopic crystals of tryptophan synthase to demonstrate that the spitrobot enables insight into catalytic events.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Alexander Klein, Petra Rovo, Varun V. Sakhrani, Yangyang Wang, Jacob B. Holmes, Viktoriia Liu, Patricia Skowronek, Laura Kukuk, Suresh K. Vasa, Peter Guentert, Leonard J. Mueller, Rasmus Linser
Summary: NMR chemical shifts provide detailed information on the chemical properties of molecules. This study demonstrates the use of higher-dimensional, proton-detected, solid-state NMR to assign a large protein, tryptophan synthase, and characterize its chemical properties and relaxation. The results suggest a connection between active-site chemistry, electrostatic environment, and catalytically important dynamics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Plant Sciences
Yousef M. Abu-Zaitoon, Ezz Al-Dein Muhammed Al-Ramamneh, Abdel Rahman Al Tawaha, Sulaiman M. Alnaimat, Fouad A. Almomani
Summary: This study aimed to investigate whether Indole synthase (INS), the first enzyme in the tryptophan-independent pathway, is involved in the tryptophan-dependent pathway. Coexpression analysis showed that INS did not show coexpression with any of the genes involved in the production of tryptophan via the chorismate pathway, suggesting its exclusive involvement in the tryptophan-independent pathway.
Article
Chemistry, Multidisciplinary
Jing Liu, Lauritz Harken, Yiling Yang, Xiulan Xie, Shu-Ming Li
Summary: This study reports two important gene clusters involved in the biosynthesis of mycocyclosin and guatyromycine. By reconstructing the biosynthetic pathways and conducting biochemical investigations, it was found that the enzymes encoded by these genes can catalyze both intramolecular oxidation and intermolecular nucleobase transfer reactions, leading to the synthesis of specific natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Cheng-xi Jiang, Jia-xing Yu, Xuan Fei, Xiao-jun Pan, Ning-ning Zhu, Chong-liang Lin, Dan Zhou, Hao-ru Zhu, Yu Qi, Zhi-gang Wu
Summary: Plant-derived monoterpene indole alkaloids (MIAs) from Uncaria rhynchophylla (UR) have significant medicinal properties in treating neurodegenerative diseases. Through metabolomics and gene expression analysis, this study identified key genes and regulators involved in the biosynthesis and regulation of MIAs in UR. Further experiments demonstrated that two specific proteins, UrSTR1 and UrSTR5, play crucial roles in the biosynthesis of MIAs. This research not only paves the way for reconstructing the biosynthesis of bioactive MIAs in other organisms but also provides valuable insights into natural product biosynthesis in medicinal plants.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Organic
Lin Chen, Jian-Wei Tang, Yan Yee Liu, Yudai Matsuda
Summary: Characterization of a biosynthetic gene cluster in the fungus Aspergillus candidus CBS 102.13 led to the discovery of a new alkaloid, aspcandine (1). The unique molecular scaffold of aspcandine (1) is synthesized by the nonribosomal peptide synthetase-polyketide synthase hybrid AcdB, which incorporates 3-hydroxy-L-kynurenine as a building block. AcdB performs chain elongation using malonyl-CoA and releases the chain to form the tricyclic system of aspcandine (1).
Review
Biochemistry & Molecular Biology
Benjamin R. Lichman
Summary: Alkaloids from plants, known for their structural diversity and bioactivity, hold a privileged position in both modern and traditional medicines. Recent research has made significant progress in elucidating the biosynthetic origins of plant alkaloids. This review focuses on the metabolic origins of true alkaloids, specialized metabolites derived from amino acids with a nitrogen heterocycle, highlighting the key roles played by modifications to primary metabolism, iminium reactivity, and spontaneous reactions in the molecular and evolutionary origins of these pathways.
NATURAL PRODUCT REPORTS
(2021)
Article
Plant Sciences
Weijia Cheng, Yan Yao, Qiuxia Wang, Xiaosa Chang, Zhuolin Shi, Xueting Fang, Fangfang Chen, Shixin Chen, Yonghong Zhang, Fan Zhang, Dongqing Zhu, Zixin Deng, Li Lu
Summary: In this study, novel BIA methyltransferases (MTs) were identified and characterized from Liriodendron chinense. Mutagenesis experiments revealed that a single-residue alteration is sufficient to change the substrate selectivity of these enzymes. This research sheds light on the molecular origin of BIAs during angiosperm evolution and provides valuable insights for the biosynthetic production of BIAs.
Editorial Material
Chemistry, Multidisciplinary
Sanath K. Kandy, Jonathan R. Chekan
Summary: While natural products from plants have been a valuable source of bioactive molecules, understanding their biosynthetic pathways has always been a challenging task. Strychnine, known for its neurotoxicity and use as a rodent pesticide, has attracted significant interest for synthesis, but little was known about its biosynthesis. A recent report from the O'Connor lab has successfully solved this long-standing puzzle by employing modern transcriptomics and transient expression techniques to identify the enzymes responsible for strychnine production, as well as an unexpected non-enzymatic step.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Plant Sciences
Ines Carqueijeiro, Konstantinos Koudounas, Thomas Duge de Bernonville, Liuda Johana Sepulveda, Angela Mosquera, Dikki Pedenla Bomzan, Audrey Oudin, Arnaud Lanoue, Sebastien Besseau, Pamela Lemos Cruz, Natalja Kulagina, Emily A. Stander, Sebastien Eymieux, Julien Burlaud-Gaillard, Emmanuelle Blanchard, Marc Clastre, Lucia Atehortua, Benoit St-Pierre, Nathalie Giglioli-Guivarc'h, Nicolas Papon, Dinesh A. Nagegowda, Sarah E. O'Connor, Vincent Courdavault
Summary: Deglycosylation is a crucial step in plant defense mechanisms, catalyzed by enzymes like SGD to produce reactive aglycones. Alternative splicing of the SGD gene in C. roseus leads to the shorter isoform shSGD, which disrupts SGD multimers and inhibits its activity, impacting downstream MIA synthesis. This pseudo-enzyme shSGD acts as a regulator of MIA biosynthesis by interfering with metabolic channeling and recruitment of enzymes.
Article
Genetics & Heredity
Jana Braesel, Janis Fricke, Daniel Schwenk, Dirk Hoffmeister
FUNGAL GENETICS AND BIOLOGY
(2017)
Review
Chemistry, Multidisciplinary
Janis Fricke, Claudius Lenz, Jonas Wick, Felix Blei, Dirk Hoffmeister
CHEMISTRY-A EUROPEAN JOURNAL
(2019)
Article
Biotechnology & Applied Microbiology
Sandra Hoefgen, Jun Lin, Janis Fricke, Maria C. Stroe, Derek J. Mattern, Johann E. Kufs, Peter Hortschansky, Axel A. Brakhage, Dirk Hoffmeister, Vito Valiante
METABOLIC ENGINEERING
(2018)
Article
Biochemistry & Molecular Biology
Felix Blei, Janis Fricke, Jonas Wick, Jason C. Slot, Dirk Hoffmeister
Article
Biochemistry & Molecular Biology
Janis Fricke, Alexander Sherwood, Robert Kargbo, Andrew Orry, Felix Blei, Andreas Naschberger, Bernhard Rupp, Dirk Hoffmeister
Article
Biochemistry & Molecular Biology
Richard Demmler, Janis Fricke, Sebastian Doerner, Markus Gressler, Dirk Hoffmeister
Article
Chemistry, Multidisciplinary
Janis Fricke, Robert Kargbo, Lars Regestein, Claudius Lenz, Gundela Peschel, Miriam A. Rosenbaum, Alexander Sherwood, Dirk Hoffmeister
CHEMISTRY-A EUROPEAN JOURNAL
(2020)
Article
Chemistry, Multidisciplinary
Felix Blei, Sebastian Doerner, Janis Fricke, Florian Baldeweg, Felix Trottmann, Anna Komor, Florian Meyer, Christian Hertweck, Dirk Hoffmeister
CHEMISTRY-A EUROPEAN JOURNAL
(2020)
Article
Plant Sciences
Janis Fricke, Alexander M. Sherwood, Adam L. Halberstadt, Robert B. Kargbo, Dirk Hoffmeister
Summary: A novel analogue of psilocybin was produced through hybrid chemoenzymatic synthesis and tested for psychedelic-like activity, showing potency between dimethyltryptamine and psilocybin.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Multidisciplinary Sciences
Benjamin H. Conlon, Cene Gostincar, Janis Fricke, Nina B. Kreuzenbeck, Jan-Martin Daniel, Malte S. L. Schlosser, Nils Peereboom, Duur K. Aanen, Z. Wilhelm de Beer, Christine Beemelmanns, Nina Gunde-Cimerman, Michael Poulsen
Summary: Insights into the genomic consequences of symbiosis for basidiomycete fungi associated with social insects are limited. Through genome analysis of termite-associated Podaxis fungi, it was found that the transition to termite association led to reductions in genome size and gene content. Termite specialists exhibited poorer performance under oxidative stress, while all lineages retained some capacity for lignin cleavage. Mitochondrial genomes of termite associates were significantly larger, potentially due to smaller population sizes or reduced competition.
Article
Biochemistry & Molecular Biology
Sebastian Doerner, Kai Rogge, Janis Fricke, Tim Schaefer, Jacob M. Wurlitzer, Markus Gressler, Duyen N. K. Pham, David R. Manke, Andrew R. Chadeayne, Dirk Hoffmeister
Summary: Genomic analysis of Psilocybe magic mushrooms reveals a diverse and unexplored secondary metabolome, providing insights into the potential pharmacological and toxicological effects associated with consumption of these mushrooms.
Article
Microbiology
Nina B. Kreuzenbeck, Elena Seibel, Jan W. Schwitalla, Janis Fricke, Benjamin H. Conlon, Suzanne Schmidt, Almuth Hammerbacher, Tobias G. Koellner, Michael Poulsen, Dirk Hoffmeister, Christine Beemelmanns
Summary: The symbiotic relationship between Macrotermitinae termites and Termitomyces fungi is essential for both partners and plays a crucial role in biomass conversion in tropical ecosystems. Research has revealed the volatile emissions and genomic features of the fungi, providing new insights into enzymatic transformations.
Article
Chemistry, Multidisciplinary
Felix Schalk, Janis Fricke, Soohyun Um, Benjamin H. Conlon, Hannah Maus, Nils Jager, Thorsten Heinzel, Tanja Schirmeister, Michael Poulsen, Christine Beemelmanns
Summary: Targeted metabolomic analysis of Pseudoxylaria sp. X187 identified two new lipopeptidic congeners, xylacremolides C and D, which showed weak histone deacetylase inhibitory and antifungal activities, as well as moderate protease inhibition activity against a panel of nine human, viral, and bacterial proteases. A putative xy gene cluster was identified from draft genome data generated by Illumina and PacBio sequencing, along with RNAseq studies.
Article
Chemistry, Multidisciplinary
Janis Fricke, Felix Blei, Dirk Hoffmeister
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2017)