Article
Chemistry, Multidisciplinary
Bo Yin, Xiaohuan Li, Zi-Xiang Li, Xiao-Xin Zhu, Lan Zhang, Xian-Li Zhou, Jin-Bu Xu, Feng-Zheng Chen, Pei Tang, Feng Gao
Summary: (-)-Adenophorone, a compound with a unique tricyclo[4.3.1.0(5,9)]decane skeleton, was isolated from Eupatorium adenopharum Spreng. Its structure was determined using spectroscopic analysis, X-ray crystallography, and bioinspired total synthesis. The synthesis of its precursor, (+)-euptox A, was achieved in 8 steps from commercially available (-)-carvone, demonstrating excellent diastereoselectivity. Bioinspired synthesis of (-)-adenophorone was achieved from a plausible biogenetic precursor via transannular Michael addition. Furthermore, compound (-)-adenophorone exhibited potent neuroprotective activity in H2O2-treated SH-SY5Y and PC12 cells.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Medicinal
Min Woo Ha, Jonghoon Kim, Seung-Mann Paek
Summary: The discovery of novel marine natural products often leads to efforts in finding new therapeutic ingredients. Due to the complexity and uniqueness of substances produced in the marine environment, there have been cases where the structures were incorrectly assigned despite the use of modern chemical techniques. Organic chemical synthesis and thorough spectroscopic data inspection are crucial in refuting inaccuracies in proposed structures.
Article
Chemistry, Multidisciplinary
Cedric Couturier, Sebastian Gross, Alexander von Tesmar, Judith Hoffmann, Selina Deckarm, Anouchka Fievet, Nelly Dubarry, Thomas Taillier, Christoph Poeverlein, Heike Stump, Michael Kurz, Luigi Toti, Sabine Haag Richter, Dietmar Schummer, Philippe Sizun, Michael Hoffmann, Ram Prasad Awal, Nestor Zaburannyi, Kirsten Harmrolfs, Joachim Wink, Emilie Lessoud, Thierry Vermat, Veronique Cazals, Sandra Silve, Armin Bauer, Michael Mourez, Laurent Fraisse, Corinne Leroi-Geissler, Astrid Rey, Stephanie Versluys, Eric Bacque, Rolf Mueller, Stephane Renard
Summary: This article describes the myxobacterial natural product Corramycin isolated from Corallococcus coralloides. Corramycin exhibits anti-Gram-negative activity against Escherichia coli and is taken up via two transporter systems. The biosynthetic gene cluster (BGC) of Corramycin was identified and a biosynthesis model was proposed. The absolute configuration of the molecule was elucidated through bioinformatic analysis and total synthesis. Animal experiments confirmed the antibacterial effect of Corramycin.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Multidisciplinary
Debobrata Paul, Ashis Kundu, Sanu Saha, Rajib Kumar Goswami
Summary: This feature article highlights total synthesis as a reliable tool for confirming the structure of natural products. Despite advances in spectroscopic techniques, structural misassignments of natural products remain common. Recent case studies have shown that chemical synthesis can be used to revise the structures of natural products.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Brandon C. Derstine, Alina J. Cook, James D. Collings, Joseph Gair, Josep Sauri, Eugene E. Kwan, Noah Z. Burns
Summary: In this study, we report the first total synthesis and full stereochemical assignment of (+)-discorhabdin V. The synthesis was achieved through a highly convergent strategy enabled by scalable access to the two key components. Our work lays the foundation for future biological evaluation of nitrogen-bridged discorhabdins.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Dan Chen, Daniel J. Park, Melissa M. Cadelis, Hana Douafer, Marie Lise Bourguet-Kondracki, Jean Michel Brunel, Brent R. Copp
Summary: Two diketopiperazine natural products were found to have antibacterial activity and enhance the action of antibiotics. However, the synthesized diastereomers did not exhibit the same properties, indicating that these compounds are not suitable templates for new treatments for microbial infections.
Article
Chemistry, Multidisciplinary
Bing-Chao Yan, Min Zhou, Jian Li, Xiao-Nian Li, Shi-Jun He, Jian-Ping Zuo, Han-Dong Sun, Ang Li, Pema-Tenzin Puno
Summary: Isoscopariusin A, isolated from Isodon scoparius, was identified as an unsymmetrical meroditerpenoid with a sterically congested carbon skeleton. Gram-scale synthesis was achieved in 12 steps, with selective inhibition of T-cell proliferation as a significant biological activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Xikang Zheng, Yan Li, Mengtie Guan, Lingyue Wang, Shilong Wei, Yi-Cheng Li, Chin-Yuan Chang, Zhengren Xu
Summary: A unified strategy for the biomimetic total synthesis of the spiroindimicin family of natural products was reported. Key transformations include one-pot two-enzyme-catalyzed oxidative dimerization and regioselective bond formation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Shingo Takiguchi, Yuki Hirota-Takahata, Takahide Nishi
Summary: The absolute configuration of ogipeptins has been elucidated by the successful total synthesis of ogipeptin A.
Article
Chemistry, Multidisciplinary
Jia-Xuan Liu, Shi-Peng Zhang, Feng-Sen Sun, Hui Li, Ya-Ling Gong, Shi-Chao Lu, Shu Xu
Summary: In this study, Naphthospironone A, a polyhydroxy cagelike bioactive natural product, was synthesized for the first time. The spiro[bicyclo[3.2.1]octane-pyran] core was constructed by an acid-promoted epoxide-opening lactonisation and a base-induced intramolecular aldol-type cyclisation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Chemistry, Multidisciplinary
Huilin Li, Jing Zhang, Xuegong She
Summary: This MiniReview demonstrates the achievements in the construction of the diquinane ring system in the past decade, discussing the strategic synthesis of the diquinane unit and its impact on the field of natural product total synthesis.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Haoran Dong, Dachao Hu, Benke Hong, Jin Wang, Xiaoguang Lei
Summary: The first total syntheses of four natural antibiotics, vermisporin, PF1052/AB4015-A, AB4015-L, AB4015-B, and one hydrogenated natural product derivative, AB4015-A2, featuring a tetramic acid bearing cis-decalin ring, are reported. The functionalized cis-decalin ring was constructed via a diastereoselective intramolecular Diels-Alder (IMDA) reaction, with a rare endo-boat transition state. The efficient installation of the sterically hindered epoxy group in vermisporin, PF1052/AB4015-A, and AB4015-L was achieved through an intramolecular neighboring-group-oriented strategy, and the desired tetramic acid structure was obtained through a one-pot aminolysis/Dieckmann condensation cascade using L-amino acid derivatives. The total synthesis allowed for the unequivocal verification of the absolute configuration of these natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Elzbieta U. Stolarczyk, Weronika Strzempek, Marta Laszcz, Andrzej Les, Elzbieta Menaszek, Krzysztof Stolarczyk
Summary: This study provides a detailed investigation into the oxidation products of TGE under different environmental conditions, revealing its oxidation mechanisms and electroactive centers, as well as evaluating its antioxidant and antitumor properties.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Saskia Schulthoff, James Y. Hamilton, Marc Heinrich, Yonghoon Kwon, Conny Wirtz, Alois Furstner
Summary: This article describes how total synthesis was used to confirm and assign the structure of cytotoxic marine macrolides, and discusses the use of modular design and catalyst-controlled transformations to achieve the preparation of stereo isomers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Multidisciplinary
Soumik De, Aritra Kumar Dan, Raghaba Sahu, Sagarika Parida, Debadutta Das
Summary: Gold catalysis is a popular and highly innovative field in catalysis research, providing new approaches for chemical transformations from simple starting materials. The application of gold catalysis in the total synthesis of natural products has successfully addressed complex challenges and achieved significant progress.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Yoshiki Asai, Tomoshige Hiratsuka, Miyu Ueda, Yumi Kawamura, Shumpei Asamizu, Hiroyasu Onaka, Manabu Arioka, Shinichi Nishimura, Minoru Yoshida
Summary: A. persicinum MF-347833 produces two ferrichrome-type siderophores with distinct biological properties, allowing it to adapt to different iron conditions.
ACS CHEMICAL BIOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Taro Ozaki, Atsushi Minami, Hideaki Oikawa
Summary: Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a class of natural products with potent biological activities, and remarkable structural diversity is generated through posttranslational modifications (PTMs). Fungal RiPPs (F-RiPPs) have fewer examples, but recent progress in sequencing of fungal genomes indicates hidden RiPP pathways in fungal resources, making F-RiPPs an attractive target for genome mining studies.
JOURNAL OF ANTIBIOTICS
(2023)
Review
Biochemistry & Molecular Biology
Taro Ozaki, Atsushi Minami, Hideaki Oikawa
Summary: In this review, the biosynthetic pathway and heterologous production of fungal indole diterpenes (IDTs) are discussed. It is found that nature's strategy involves a two-stage synthesis for the core scaffold and platform intermediates, and late-stage modifications for installing an additional cyclic system on the indole ring. The potential of applying this strategy in the synthesis of highly elaborated IDTs and future biosynthetic engineering is also addressed.
NATURAL PRODUCT REPORTS
(2023)
Article
Chemistry, Organic
Yaping Liu, Taro Ozaki, Atsushi Minami, Hideaki Oikawa
Summary: Oxidative modifications are essential for the biosynthesis of indole diterpenes (IDTs), and this study focused on the role of prenyltransferases and flavoprotein oxidases in the synthesis of nodulisporic acid-type and shearinine-type bicyclic rings on the indole moiety. The enzymatic reaction of prenyltransferase JanD showed that it recognizes a C13 hydroxy group on the diterpene moiety. Flavoprotein oxidases JanO and NodO exhibited different substrate specificities for penta/hexacyclic IDTs and pentacyclic IDTs, respectively.
TETRAHEDRON LETTERS
(2023)
Article
Biotechnology & Applied Microbiology
Yukun Lei, Shumpei Asamizu, Takumi Ishizuka, Hiroyasu Onaka
Summary: Recent (meta)genomics studies have revealed the bacterial metabolic potential to synthesize diverse secondary metabolites in the environment, showing that bacteria are continuously exposed to harmful chemical compounds. Streptomyces spp. produce bioactive secondary metabolites and have evolved membrane transport systems to protect against antibiotics. A study on a mutant of Streptomyces coelicolor identified a point mutation in the sco1718 gene, which reduced secondary metabolite production. Inactivation of the sco1718 gene resulted in decreased expression of two-component ABC transporter genes and increased antibiotic resistance.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2023)
Article
Chemistry, Medicinal
Shinta Ijichi, Shotaro Hoshino, Shumpei Asamizu, Hiroyasu Onaka
Summary: We discovered solabiomycins, a new class of lipopeptides with polar-functionalized fatty acyl groups, through genome mining and stable isotope labeling. These solabiomycins contain a sulfoxide group in the labionin moiety called solabionin. Our study demonstrated that the sulfoxide is critical for the antibacterial activity of solabiomycins against Gram-positive bacteria. We also characterized the catalytic activity of SolS, which is involved in the sulfoxidation of solabionin, and determined its role in converting deoxysolabiomycins to solabiomycins.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Plant Sciences
Sho Furumura, Taro Ozaki, Akihiro Sugawara, Yohei Morishita, Kento Tsukada, Tatsuya Ikuta, Asuka Inoue, Teigo Asai
Summary: By mining fungal genomic information, a non-canonical iterative type I PKS with an N-terminal adenylation-thiolation didomain was found to catalyze the formation of naringenin chalcone. Analysis suggested the involvement of a C-terminal thioesterase domain in Claisen-type cyclization. Furthermore, an enzyme responsible for the biosynthesis of (2S)-flavanone in fungal flavonoids was also identified. These findings reveal novel fungal biosynthetic processes leading to plant-like metabolites.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Microbiology
Toshiki Nagakubo, Shumpei Asamizu, Tatsuya Yamamoto, Manami Kato, Tatsuya Nishiyama, Masanori Toyofuku, Nobuhiko Nomura, Hiroyasu Onaka
Summary: We found that Streptomyces lividans produces intracellular CIS-like nanostructures (Streptomyces phage tail-like particles [SLPs]) that affect the phenotypes of this bacterium under hyperosmotic conditions. These SLPs are localized in the cytoplasm and their loss leads to delayed aerial mycelia erection and decreased growth. SLPs are associated with a protein interaction network within the cytoplasm, including interactions with ribosomal proteins and translation elongation factors.
Article
Chemistry, Multidisciplinary
Shotaro Hoshino, Shinta Ijichi, Shumpei Asamizu, Hiroyasu Onaka
Summary: Recently, the unique bioactivities of arsenic-containing secondary metabolites have been discovered, but studies on arsenic secondary metabolism in microorganisms are limited. In this study, we focused on an unknown arsenic metabolite called bisenarsan, produced by well-studied actinomycetes, and elucidated its structure through feeding experiments and detailed NMR analyses. Bisenarsan is the first characterized arsenic secondary metabolite derived from actinomycetes and could potentially serve as a prototoxin or a detoxification product. We also confirmed the genes responsible for bisenarsan biosynthesis, particularly the (2-hydroxyethyl)arsonic acid moiety. Notably, we proposed a novel mechanism for the formation of a C-As bond in bisenarsan through intramolecular rearrangement by a phosphoglycerate mutase homologue, which is distinct from the conventional As-alkylation mechanism. Our findings will accelerate the development of arsenic natural product biosynthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Akihisa Matsuyama, Atsushi Hashimoto, Shinichi Nishimura, Minoru Yoshida
Summary: Considering the frequent use of leu1 and ura4 genes in fission yeast, we developed new host-vector systems by editing lys1 and arg3 genes with the CRISPR/Cas9 system. We obtained critical mutations in the ORF region and developed complementary vectors for lys1 and arg3 mutants. By combining these vectors with the integration vector pDUAL, we successfully visualized the localization of three proteins fused with different fluorescent proteins in a single cell. Thus, these vectors enable combinatorial expression of heterologous genes, addressing the increasingly diverse experimental challenges.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Fumihiro Ishikawa, Natsumi Tsukumo, Erika Morishita, Shumpei Asamizu, Saaya Kusuhara, Shinsuke Marumoto, Katsuki Takashima, Hiroyasu Onaka, Genzoh Tanabe
Summary: We present a method called activity-based protein profiling for studying the adenylation domains of non-ribosomal peptide synthetases (ABPP-NRPS) in bacterial proteomes. This method allows substrate tolerance towards non-proteinogenic amino acids by using a range of non-proteinogenic amino acid sulfamoyladenosines in a competitive format. Additionally, we demonstrate successful incorporation of a non-proteinogenic amino acid (O-allyl-L-serine) into gramicidin S using precursor-directed biosynthesis.
CHEMICAL COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Taro Ozaki
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2023)
Article
Biochemical Research Methods
Mayuki Sasaki, Shinichi Nishimura, Akihisa Matsuyama, Minoru Yoshida
Summary: This protocol describes the process of synthesizing isoleucine from threonine by measuring the enzymatic activity of threonine deaminase in fission yeast cell lysate. The enzymatic activity is catalyzed by Tda1. The protocol involves preparing cell lysates from fission yeast cell cultures and measuring threonine deaminase activity using threonine or serine as a substrate.
