Article
Microbiology
Bruna Domingues Vieira, Henrique Niero, Rafael de Felicio, Luiz Fernando Giolo Alves, Cristina Freitas Bazzano, Renata Sigrist, Luciana Costa Furtado, Gabriela Felix Persinoti, Leticia Veras Costa-Lotufo, Daniela Barretto Barbosa Trivella
Summary: Streptomyces sp. BRA-346 is a type of actinobacteria isolated from the Brazilian endemic tunicate Euherdmania sp. Research has shown that this strain produces epoxyketone peptides, which inhibit proteasome activity and exhibit high cytotoxicity to glioma cells. However, the low yields and poor reproducibility of epoxyketone peptides production by BRA-346 under laboratory conditions have hindered further studies. By evaluating different cultivation methods, culture media, and chemical elicitors, as well as sequencing the BRA-346 genome and using metabolomics, researchers have demonstrated the potential of BRA-346 to produce epoxyketone peptides and shed light on its regulatory mechanisms.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Chemistry, Medicinal
Takayoshi Awakawa
Summary: Natural products are a vital source for medicinal purposes. Recent research has focused on discovering novel biosynthetic enzymes and engineering enzymes to produce unnatural bioactive compounds.
CHEMICAL & PHARMACEUTICAL BULLETIN
(2021)
Review
Oncology
Priyanka S. Rana, James J. Ignatz-Hoover, James J. Driscoll
Summary: Proteasomes are complex protein-degrading machines that regulate the elimination of intracellular proteins. Immunoproteasomes are a specialized variant that degrade proteins in cells exposed to oxidative stress and inflammation. They can be targeted for therapeutic purposes in the treatment of cancer and infectious diseases.
Article
Plant Sciences
Minghua Wei, Ying Huang, Changjuan Mo, Haiyan Wang, Qingguo Zeng, Wenli Yang, Jihao Chen, Xuejun Zhang, Qiusheng Kong
Summary: By assembling and projecting published QTLs onto the assembled Kuizilikjiz genome, this study has expanded the high-quality genome resources and provided valuable QTL information for gene cloning of important traits in melon.
HORTICULTURE RESEARCH
(2023)
Review
Chemistry, Multidisciplinary
Divas Kumar, A. K. Narula, Deepa Deswal
Summary: This article discusses the role of fungal enzymes in the synthesis of various drugs, active pharmaceutical ingredients (API), and drug intermediates, as well as their applications in the pharmaceutical industry. Fungal enzymes have scalability, high catalytic activity, relatively low cost, and the ability to catalyze a wide range of chemical reactions under mild reaction conditions, making them valuable in pharmaceutical synthesis.
Article
Multidisciplinary Sciences
Jialiang Wang, Jingdan Liang, Lu Chen, Wei Zhang, Liangliang Kong, Chao Peng, Chen Su, Yi Tang, Zixin Deng, Zhijun Wang
Summary: Statins, effective cholesterol-lowering drugs, depend on a megasynthase complex for biosynthesis. CryoEM structures of LovB-LovC and core LovB provide insights into the catalytic cycle for lovastatin production.
NATURE COMMUNICATIONS
(2021)
Review
Agronomy
Duo Xia, Hao Zhou, Yipei Wang, Pingbo Li, Pei Fu, Bian Wu, Yuqing He
Summary: Anthocyanins play an important role in the diverse colors of organs in rice, with their accumulation being related to the domestication process. Understanding the genetic basis of anthocyanin biosynthesis in rice is crucial for breeding novel rice cultivars.
Review
Biochemistry & Molecular Biology
Parinita Singh, Pratibha Shukla, A. K. Narula, Deepa Deswal
Summary: The increasing number of diseases in the past decade has emphasized the importance of researching and developing new drugs. Malignant diseases and life-threatening microbial infections have become more prevalent, causing high mortality rates and a rise in drug-resistant microbes. Biological macromolecules derived from carbohydrates and lipids have been found to be effective in treating infections and diseases. These macromolecules offer diverse chemical properties that can be manipulated for drug synthesis. This review highlights their role and significance by discussing various reactions and pathways reported in the literature.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Laura Ielo, Vincenzo Patamia, Andrea Citarella, Thomas Efferth, Nasim Shahhamzehei, Tanja Schirmeister, Claudio Stagno, Thierry Langer, Antonio Rescifina, Nicola Micale, Vittorio Pace
Summary: This study reports a new class of anti-cancer compounds that selectively inhibit proteasome activity, and show potential for inhibiting cancer cell proliferation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Markus Klein, Michael Busch, Manja Friese-Hamim, Stefano Crosignani, Thomas Fuchss, Djordje Musil, Felix Rohdich, Michael P. Sanderson, Jeyaprakashnarayanan Seenisamy, Gina Walter-Bausch, Ugo Zanelli, Philip Hewitt, Christina Esdar, Oliver Schadt
Summary: Proteasomes are essential components of the ubiquitin-dependent protein degradation pathway, with LMP7 being a subunit of the immunoproteasome. Current pan-proteasome inhibitors nonselectively target LMP7 and other subunits, limiting their therapeutic applicability. Novel amido boronic acids were discovered to selectively inhibit LMP7, leading to the identification of the highly potent and orally available inhibitor M3258, which showed strong antitumor activity in MM models.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Andressa Barban do Patrocinio, Vanderlei Rodrigues, Lizandra Guidi Magalhaes
Summary: This review discusses the mechanism of protein p53 degradation through the ubiquitin-proteasome system, and how compounds inhibiting the 26S proteasome can treat cancer and other diseases by regulating the stability of p53.
Article
Biochemistry & Molecular Biology
Hao Zhou, Duo Xia, Pingbo Li, Yiting Ao, Xiaodong Xu, Shanshan Wan, Yanhua Li, Bian Wu, Huan Shi, Kaiyue Wang, Guanjun Gao, Qinglu Zhang, Gongwei Wang, Jinghua Xiao, Xianghua Li, Sibin Yu, Xingming Lian, Yuqing He
Summary: This study conducted a genome-wide association study on oil composition and concentration in 533 cultivated rice accessions, identifying 46 loci significantly associated with grain oil traits and 26 candidate genes involved in oil metabolism. Specific haplotypes of PAL6 and LIN6 have been selected in japonica rice, indicating natural variation in oil composition. These findings provide new insights into the genetic basis of oil biosynthesis in rice grains and can aid in marker-based breeding for enhanced oil and grain quality.
Article
Biochemistry & Molecular Biology
Lei Zhao, Camille Le Chapelain, Alexander O. Brachmann, Marcel Kaiser, Michael Groll, Helge B. Bode
Summary: This study reveals the production and identification of GLNPs in the native host after activation of the silent BGC, as well as the chemical diversity and correlation with the crystal structure of the yeast proteasome, providing a basis for engineering the BGC to generate new GLNPs and optimize these natural products for potential cancer therapy.
Article
Multidisciplinary Sciences
Kota Ichimaru, Koji Yamaguchi, Kenichi Harada, Yusaku Nishio, Momoka Hori, Kazuya Ishikawa, Haruhiko Inoue, Shusuke Shigeta, Kento Inoue, Keita Shimada, Satomi Yoshimura, Takumi Takeda, Eiki Yamashita, Toshimichi Fujiwara, Atsushi Nakagawa, Chojiro Kojima, Tsutomu Kawasaki
Summary: The U-box type ubiquitin ligase PUB44 positively regulates pattern-triggered immunity in rice by degrading the protein PBI1, which in turn activates the WRKY45 transcription factor. The activation of WRKY45 by chitin is regulated by the coordination between MAP kinase-mediated phosphorylation and PUB44-mediated degradation of PBI1.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Hyunsung Nam, Joon Soo An, Jaepil Lee, Yonghwan Yun, Hyunbin Lee, Hyungou Park, Yousung Jung, Ki-Bong Oh, Dong-Chan Oh, Seokhee Kim
Summary: This study demonstrates the ability of cytochrome P450 enzymes to generate diverse biaryl linkages, expanding the chemical diversity of macrocyclic peptides. Using genome mining and NMR structure determination, the study identified three unprecedented or rare biaryl linkages. The findings are significant for exploring the chemical structures of biaryl-containing peptides encoded in bacterial genomes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Trevor N. Purdy, Min Cheol Kim, Reiko Cullum, William Fenical, Bradley S. Moore
Summary: This study reports a new metabolic deviation in benzylic dehydrogenation reaction, revealing a new synthesis pathway for organic chlorinated compounds. By heterologous expression of oxidoreductase enzymes, divergent oxidative dehydrogenation and pyrrolizine-forming reactions were supported.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Tristan de Rond, Julia E. Asay, Bradley S. Moore
Summary: A genome-mining approach was developed to discover biochemical transformations through the analysis of co-occurring enzyme domains in a single protein. This methodology successfully identified new enzymatic activities and provided functional annotation for multidomain enzymes.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Plant Sciences
Trevor N. Purdy, Bradley S. Moore, April L. Lukowski
Summary: The utilization of ortho-quinone methide (o-QM) intermediates in complex molecule assembly is an efficient strategy designed by Nature and utilized by synthetic chemists. The biosynthetic enzymes that generate o-QMs have great potential for biocatalytic applications, enabling the selective production of desirable compounds that are otherwise difficult to achieve by traditional synthetic methods. Further characterization of these enzymes may lead to the discovery of new enzymes capable of similar chemistry on diverse substrates.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Chemistry, Multidisciplinary
Sanjoy Adak, April L. Lukowski, Rebecca J. B. Schafer, Bradley S. Moore
Summary: AETX is a neurotoxin that is deadly to bald eagles in the United States. A recently discovered biosynthetic pathway converts two molecules of tryptophan to AETX using five enzymes, including novel enzymes with unique biochemical functions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Page N. Daniels, Hyunji Lee, Rebecca A. Splain, Chi P. Ting, Lingyang Zhu, Xiling Zhao, Bradley S. Moore, Wilfred A. van der Donk
Summary: This study identified a new biosynthetic pathway in which glycyl-tRNA is used to attach amino acids to a ribosomally synthesized peptide, generating amino acid-derived natural products. This pathway involves multiple hydroxylations and chemical modifications.
Article
Chemistry, Organic
Oussama Yahiaoui, Lauren A. M. Murray, Fengyue Zhao, Bradley S. Moore, Kendall N. Houk, Fang Liu, Jonathan H. George
Summary: We report the first example of a diazo-Hooker reaction, which involves the formation of a phthalazine ring system by the oxidative rearrangement of a diazoketone. Computational studies revealed the reaction mechanism, and a related natural product was used to mimic the biosynthetic origin of the diazoketone functional group.
Article
Multidisciplinary Sciences
Taylor S. Steele, John K. Brunson, Yukari Maeno, Ryuta Terada, Andrew E. Allen, Mari Yotsu-Yamashita, Jonathan R. Chekan, Bradley S. Moore
Summary: The biosynthetic pathways of domoic acid differ between diatoms and red macroalgae, with the absence of a critical enzyme in red macroalgae. Red macroalgae produce domoic acid via isodomoic acid B, with a unique origin of the rad genes compared to diatoms. The production of domoic acid in diatoms and red macroalgae involves a combination of native eukaryotic CYP450 neofunctionalization and horizontal gene transfer.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Katherine D. Bauman, Vikram V. Shende, Percival Yang-Ting Chen, Daniela B. B. Trivella, Tobias A. M. Gulder, Sreekumar Vellalath, Daniel Romo, Bradley S. Moore
Summary: This study reports an enzymatic route to the salinosporamide core and reveals the catalytic role of a ketosynthase, SalC, in transacylation and bond-forming reactions. The crystal structure of SalC and site-directed mutagenesis studies proposed a bicyclization reaction mechanism. This work challenges our understanding of ketosynthase enzymes and provides a foundation for the streamlined production of clinically relevant chemotherapeutics in the future.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Immo Burkhardt, Tristan de Rond, Percival Yang-Ting Chen, Bradley S. Moore
Summary: Octocorals contribute significantly to the chemical diversity of terpenoids in the ocean. Contrary to the conventional belief that natural products in sessile marine animals are primarily synthesized by symbiotic microbes, this study provides evidence of a monophyletic lineage of animal-encoded terpene cyclases (TCs) present in octocorals. The study identified several TC enzymes in octocorals that produce precursors of specific terpenoids unique to corals. The research highlights the biosynthetic capacity of the Animalia kingdom, comparable to plants, and suggests the biotechnological potential of octocorals for biomedical applications.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jennifer H. Wisecaver, Robert P. Auber, Amanda L. Pendleton, Nathan F. Watervoort, Timothy R. Fallon, Olivia L. Riedling, Schonna R. Manning, Bradley S. Moore, William W. Driscoll
Summary: Harmful algal blooms of the toxic haptophyte Prymnesium parvum are a recurrent problem in many inland and estuarine waters around the world. Genomic analysis of 15 diverse strains of P. parvum revealed considerable DNA content variation and identified functional categories associated with metabolic and genome size variation. The results indicate the presence of multiple cryptic species within P. parvum and highlight the need for similar resources for other harmful algal-bloom-forming morphospecies.
Article
Chemistry, Multidisciplinary
April L. Lukowski, Felix M. Hubert, Thuan-Ethan Ngo, Nicole E. Avalon, William H. Gerwick, Bradley S. Moore
Summary: We report the discovery and characterization of an alkynyl halogenase, JamD, which is capable of terminal alkyne halogenation and has broad substrate tolerance. This finding has significant implications for the development of chemoselective biocatalysts, such as the synthesis of haloalkynes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Microbiology
Amanda T. Alker, Morgan V. Farrell, Alpher E. Aspiras, Tiffany L. Dunbar, Andriy Fedoriouk, Jeffrey E. Jones, Sama R. Mikhail, Gabriella Y. Salcedo, Bradley S. Moore, Nicholas J. Shikuma
Summary: In this study, a modular plasmid toolkit was adapted for use in 12 marine bacteria, and a marine Pseudoalteromonas bacterium was successfully engineered to study its association with its host animal. This work demonstrates the potential of modular genetic tools to be applied to diverse marine bacteria for basic science research and biotechnology innovations.
Article
Chemistry, Physical
Jennifer L. L. Cordoza, Percival Yang-Ting Chen, Linnea R. R. Blaustein, Stella T. T. Lima, Marli F. F. Fiore, Jonathan R. R. Chekan, Bradley S. S. Moore, Shaun M. K. McKinnie
Summary: Researchers have discovered and characterized the biosynthetic pathway of guanitoxin, a neurotoxin containing a cyclic arginine derivative. By comparing the structures and activities, they have identified the amino acid residues that contribute to the catalytic mechanism. This study provides a better understanding of how nature produces cyclic arginine noncanonical amino acids and offers tools for their biocatalytic production and biological applications.
Article
Ecology
Amanda T. Alker, Morgan V. Farrell, Alyssa M. Demko, Trevor N. Purdy, Sanjoy Adak, Bradley S. Moore, Jennifer M. Sneed, Valerie J. Paul, Nicholas J. Shikuma
Summary: The quality of bacteria associated with corals and coral reefs is crucial for coral fitness, as bacteria can stimulate the transition from larval to juvenile life cycle in corals. This study investigates the role of Tetrabromopyrrole (TBP), a small molecule produced by bacteria, in coral metamorphosis. The results show that the gene bmp2 is critical for TBP biosynthesis in the bacteria and its mutation affects the ability of the bacteria to stimulate coral metamorphosis. This study provides new genetic techniques to explore coral-bacteria interactions and has implications for coral restoration.
ISME COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Katherine D. Bauman, Keelie S. Butler, Bradley S. Moore, Jonathan R. Chekan
Summary: With the availability of genetic information for hundreds of thousands of organisms in publicly accessible databases, scientists have unprecedented opportunities to explore the diversity and inner workings of life. By harnessing this information, researchers are able to specifically discover bioactive natural products and their gene clusters using orthogonal genome mining strategies.
NATURAL PRODUCT REPORTS
(2021)