Article
Chemistry, Multidisciplinary
Amy E. Fraley, Cora L. Dieterich, Mathijs F. J. Mabesoone, Hannah A. Minas, Roy A. Meoded, Franziska Hemmerling, Joern Piel
Summary: This study provides the first structural insights into a distinct group of TEs (TE(B)s) that have diverse acylation roles in polyketide and peptide biosynthesis. By analyzing and engineering the active site, the acyl-group acceptance can be modulated. Moreover, the production of longer chain branched oocydins was discovered, positioning this enzyme as a valuable synthetic biology tool for polyketide drug development.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Yaojie Gao, Yuchun Zhao, Jie Zhou, Maohua Yang, Lin Lin, Wenning Wang, Meifeng Tao, Zixin Deng, Ming Jiang
Summary: The study investigated the biosynthetic pathway of type II polyketide murayaquinone, focusing on the role of MrqM in the second polyketide ring cyclization. Results from gene deletion experiments and structural elucidation of intermediates showed that MrqM is essential for the proper biosynthesis of murayaquinone. Additionally, it was suggested that MrqD, previously thought to be involved in ring cyclization, might actually play a different role in the chain releasing step of murayaquinone biosynthesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
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
Chemistry, Multidisciplinary
Myoun-Su Kim, Munhyung Bae, Ye-Eun Jung, Jung Min Kim, Sunghoon Hwang, Myoung Chong Song, Yeon Hee Ban, Eun Seo Bae, Suckchang Hong, Sang Kook Lee, Sun-Shin Cha, Dong-Chan Oh, Yeo Joon Yoon
Summary: The biosynthesis of cyclodepsipeptide WS9326A in Streptomyces sp. SNM55 involves unprecedented nonlinear NRPS assembly processes, including the shuttling of activated amino acids mediated by TE enzymes, the independent operation of C-T didomain modules, and the first example of module skipping.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Ting Tang, Lihao Fu, Wenhao Xie, Yizhou Luo, Yating Zhang, Jianzhi Zhang, Tong Si
Summary: Rhamnolipids (RLs) are bio-surfactants derived from Pseudomonas aeruginosa, and their molecular structure plays a major role in their properties. Rhamnosyltransferase 1 chain A (RhlA) is involved in RL lipid synthesis, but its catalytic mechanism and relationship with structure and function are not well understood. This study presents the crystal structure of P. aeruginosa RhlA and reveals a surprising presence of free fatty acids, which are reaction intermediates in RL synthesis. Mutations targeting different ligand-binding pockets also affect RL production. This research provides insights for engineering RL biosynthesis.
Article
Chemistry, Physical
Ting Tang, Lihao Fu, Wenhao Xie, Yizhou Luo, Yating Zhang, Jianzhi Zhang, Tong Si
Summary: Rhamnolipids (RLs) are a desirable class of bioferase and the catalytic mechanism and sequence-structure-function relationship of RhlA were investigated. It was found that free fi-hydroxy fatty acids are a reaction intermediate during HAA synthesis.
Article
Chemistry, Physical
Jiahui Yu, Juan Song, Changbiao Chi, Tan Liu, Tongtong Geng, Zonghui Cai, Weidong Dong, Cheng Shi, Xueyang Ma, Zhongyi Zhang, Xiaojie Ma, Baiying Xing, Hongwei Jin, Liangren Zhang, Suwei Dong, Donghui Yang, Ming Ma
Summary: The bifunctional thioesterase domain Skyxy-TE catalyzes both epimerization and cyclization in skyllamycin biosynthesis. The crystal structure of Skyxy-TE was solved, revealing key residues involved in the reactions and facilitating future studies in chemoenzymatic synthesis or combinatorial biosynthesis.
Article
Biology
Luis E. Valencia, Matthew R. Incha, Matthias Schmidt, Allison N. Pearson, Mitchell G. Thompson, Jacob B. Roberts, Marina Mehling, Kevin Yin, Ning Sun, Asun Oka, Patrick M. Shih, Lars M. Blank, John Gladden, Jay D. Keasling
Summary: Researchers have successfully engineered P. putida to produce medium- and long-chain free fatty acids (FFAs) using functional genomics. They also developed a strategy to control the chain length of FFAs, resulting in a strain specialized in producing medium-chain FFAs. Furthermore, these strains were able to synthesize medium-chain fatty acid methyl esters, which have potential application as biodiesel blending agents.
COMMUNICATIONS BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Kaho Sogahata, Taro Ozaki, Yuya Igarashi, Yuka Naganuma, Chengwei Liu, Atsushi Minami, Hideaki Oikawa
Summary: UstYa family proteins are widely distributed in fungi and are involved in the biosynthesis of peptides. Three UstYa homologues were found to be crucial for desaturation of amino acid moieties, displaying unique functions. Further research could lead to the discovery of novel fungal metabolites with unique modifications.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Xiaojun Li, Ryo Shimaya, Tohru Dairi, Wei-chen Chang, Yasushi Ogasawara
Summary: The study identified the biosynthetic pathways of peptide natural products Hormaomycins and Belactosins, revealing a novel pathway for cyclopropane ring construction and exemplifying new chemistry involving metalloenzymes in natural product biosynthesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Multidisciplinary Sciences
Dake Liu, Garret M. Rubin, Dipesh Dhakal, Manyun Chen, Yousong Ding
Summary: Peptidic natural products (PNPs) serve as a valuable source of lead compounds for drug discovery, but their chemical synthesis faces challenges such as the unavailability of constituent amino acids. Advances in biosynthesis and biocatalysis offer a promising alternative for the synthesis of PNPs.
Article
Multidisciplinary Sciences
Florian Hubrich, Nina M. Bosch, Clara Chepkirui, Brandon Morinaka, Michael Rust, Muriel Gugger, Serina L. Robinson, Anna L. Vagstad, Jorn Piel
Summary: Lipopeptides are a group of microbial natural products that are important for their antibacterial and antifungal properties, as well as their strong biosurfactant effects. Most lipopeptides consist of cyclic peptides with various fatty acyl groups at the N-terminus. In this study, ribosomally derived lipopeptides called selidamides were discovered through genome-guided approaches. These selidamides were found to be widely distributed across different bacterial phyla and have cyclic peptide moieties with fatty acyl units attached to ornithine or lysine side chains. Unlike nonribosomal lipopeptides, selidamides are selectively acylated with different fatty acids. This study highlights the ability of ribosomal pathways to produce diverse lipopeptides and expands the potential for peptide drug development and targeted discovery.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Green & Sustainable Science & Technology
Ananya Satapathy, Kankana Saikia, Samuel Lalthazuala Rokhum
Summary: Greener methods for the production of nanoparticles have been explored in this study, with a focus on synthesizing CaO nanoparticles using banana leaf extracts. The CaO nanoparticles were successfully obtained through calcination of calcium hydroxide obtained from the precursor calcium nitrate. The synthesized CaO nanoparticles showed high catalytic activity in the transesterification of soybean oil, achieving a conversion rate of 98.0% under the optimal reaction conditions.
Article
Microbiology
Jessica Zampolli, Alessandra De Giani, Alessandra Di Canito, Guido Sello, Patrizia Di Gennaro
Summary: In this study, a novel biosurfactant with antimicrobial properties was isolated from Rhodococcus opacus R7. The biosurfactant was classified as a hydrophobic peptide and showed antimicrobial activity against Escherichia coli and Staphylococcus aureus.
Review
Food Science & Technology
V. H. Urrutia-Baca, S. N. Hernandez-Hernandez, L. M. Martinez, J. P. Davila-Vega, C. Chuck-Hernandez
Summary: Probiotics are widely used in functional foods, but their potential application in food fortification has not been extensively discussed. This review focuses on the products that probiotics can produce and their effect on nutritional value in specific conditions. It also discusses the recent data on how probiotics in dairy foods can convert minerals into amino acids, synthesize B-complex vitamins and peptides, and the methods for measuring these modifications.
FOOD REVIEWS INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Kazuya Yamanaka, Hibiki Fukumoto, Naoki Yoshimura, Kenji Arakawa, Yasuo Kato, Yoshimitsu Hamano, Tadao Oikawa
Summary: This study reports the rational discovery of an unexplored cationic homo polyamino acid (CHPA) antibiotic through genome mining, which showed excellent antimicrobial activity against a broad spectrum of microorganisms including bacteria and fungi, as well as resistance against nonspecific proteolytic enzymes. This marks the first efficacy report of the strain prioritization-guided genome mining strategy for the discovery of bioactive CHPAs.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tadao Oikawa, Kouhei Okajima, Kazuya Yamanaka, Shiro Kato
Summary: We successfully expressed selenocysteine beta-lyase (Lm-SCL) from Leuconostoc mesenteroides LK-151 in soluble fractions of Escherichia coli. Lm-SCL showed high preference for L-selenocysteine and had enough catalytic efficiency. It had optimal temperature and pH and remained stable under certain conditions.
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
Takaki Okamoto, Kazuya Yamanaka, Yoshimitsu Hamano, Shingo Nagano, Tomoya Hino
Summary: In this study, the crystal structure of the adenylation domain of epsilon-PL synthetase was determined, providing insights into the precise interactions between the enzyme and L-Lys and its analogs. The findings contribute to a better understanding of the epsilon-PL synthesis mechanism and have implications for the successful application of NRPS adenylation domains in bioengineering.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(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)
