Article
Chemistry, Physical
Richiro Ushimaru, Ikuro Abe
Summary: This review summarizes recent discoveries that have significantly expanded our understanding of unusual nonheme iron enzyme catalysis in natural product biosynthesis.
Review
Chemistry, Medicinal
Richiro Ushimaru
Summary: This review summarizes our current understanding of how α-ketoglutarate-dependent nonheme iron enzymes catalyze the formation of epoxides, aziridines, and cyclopropanes in nature, which are found in various medicinal natural products.
JOURNAL OF NATURAL MEDICINES
(2023)
Article
Biotechnology & Applied Microbiology
Longhai Dai, Xiao Zhang, Yumei Hu, Jing Shen, Qi Zhang, Lilan Zhang, Jian Min, Chun-Chi Chen, Yingle Liu, Jian-Wen Huang, Rey-Ting Guo
Summary: This study provides valuable insights into the catalytic selectivity of AdeV, a carrier protein-independent nonheme iron- and alpha-ketoglutarate (alpha KG)-dependent halogenase (NHFeHaI), and will facilitate the rational engineering of AdeV and other NHFeHals for synthesis of halogenated nucleotides.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Monica E. Neugebauer, Elijah N. Kissman, Jorge A. Marchand, Jeffrey G. Pelton, Nicholas A. Sambold, Douglas C. Millar, Michelle C. Y. Chang
Summary: Researchers have developed a strategy to expand enzymatic halogenation by engineering a reaction pathway rather than substrate selectivity. They discovered active halogenases from a DNA shuffle library and engineered a hydroxylase to perform halogenation with comparable activity and higher selectivity than the wild-type halogenase, showcasing the potential of harnessing hydroxylases for biocatalytic halogenation.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Xinyang Li, Takayoshi Awakawa, Takahiro Mori, Meiqi Ling, Dan Hu, Bin Wu, Ikuro Abe
Summary: In this study, the biosynthetic pathway of a group of six-cyclic meroterpenoids isolated from marine fungus was investigated. Through heterologous expression and enzyme assays, a heterodimer of NHI proteins was found to play a key role in catalyzing multiple oxidation steps, shedding light on a novel methodology for oxygenase structures in secondary metabolite biosynthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Yun Ji Park, Richard J. Jodts, Jeffrey W. Slater, Reyvin M. Reyes, Valerie J. Winton, Rana A. Montaser, Paul M. Thomas, William B. Dowdle, Anahi Ruiz, Neil L. Kelleher, J. Martin Bollinger, Carsten Krebs, Brian M. Hoffman, Amy C. Rosenzweig
Summary: The iron-containing heterodimeric MbnBC enzyme complex plays a central role in the biosynthesis of methanobactins (Mbns) and its active species is a mixed-valent, antiferromagnetically coupled Fe(II)Fe(III) center. MbnC is also involved in recognition of the MbnA leader peptide.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Ryusei Matsumoto, Saho Yoshioka, Miho Yuasa, Yoshitsugu Morita, Genji Kurisu, Nobutaka Fujieda
Summary: We repurposed a cupin superfamily protein's metal-binding site into a 2-His-1-carboxylate facial triad to create artificial metalloenzymes capable of catalyzing new reactions. The Cu2+-H52A/H58E variant was able to catalyze a stereoselective Michael addition reaction and had a flexible metal-binding site in its crystal structure. Additionally, the H52A/H58E/F104W mutant accommodated a water molecule, leading to high stereoselectivity through hydrogen bonding. Thus, the 2-His-1-carboxylate facial triad is a versatile and promising metal-binding motif for both abiological and canonical biological reactions.
Article
Chemistry, Multidisciplinary
Mengting Liu, Masao Ohashi, Qingyang Zhou, Jacob N. Sanders, Erin P. Mccauley, Phillip Crews, K. N. Houk, Yi Tang
Summary: We have discovered and reconstructed a concise biosynthetic pathway of the strained dipeptide (+)-azonazine A using Aspergillus insulicola from marine sources. A P450 enzyme catalyzes the formation of the hexacyclic benzofuranoindoline ring system from cyclo-(L-Trp-N-methyl-L-Tyr) through oxidative cyclization. Supplementing the producing strain with different indole-substituted tryptophan derivatives resulted in the production of a series of azonazine A analogs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Mengting Liu, Masao Ohashi, Qingyang Zhou, Jacob N. Sanders, Erin P. McCauley, Phillip Crews, K. N. Houk, Yi Tang
Summary: We uncovered the biosynthetic pathway of (+)-azonazine A and generated a series of analogs through supplementation of indole-substituted tryptophan derivatives.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Plant Sciences
Jiao-Jiao Song, Xin Fang, Chen-Yi Li, Yan Jiang, Jian-Xu Li, Sheng Wu, Juan Guo, Yan Liu, Hang Fan, Yan-Bo Huang, Yu-Kun Wei, Yu Kong, Qing Zhao, Jing-Jing Xu, Yong-Hong Hu, Xiao-Ya Chen, Lei Yang
Summary: A 2-oxoglutarate-dependent dioxygenase (2-ODD) gene responsible for tanshinone IIA biosynthesis in Salvia miltiorrhiza was identified in this study. The gene, known as Sm2-ODD14, acts as a dehydrogenase and catalyzes the aromatization of the furan ring. The study also showed that Sm2-ODD14 controls the metabolite flux from dihydrofuran- to furan-tanshinones, which impacts the medicinal properties of S. miltiorrhiza.
Article
Biochemistry & Molecular Biology
Jenna M. Greve, Andrew M. Pinkham, Zechariah Thompson, J. A. Cowan
Summary: HAAH is an important enzyme that binds both iron and calcium in its active site, with both metals playing different roles in enzyme stability and activity. Through experimental analysis, the importance of metal binding sites was discovered, along with the identification of a previously unreported residue crucial for HAAH catalysis.
Article
Chemistry, Inorganic & Nuclear
Abhijit Bera, Debobrata Sheet, Tapan Kanti Paine
Summary: This study synthesized and characterized two mononuclear nonheme iron(ii)-benzoylformate complexes with tridentate nitrogen donor ligands, and investigated their bioinspired oxidation performance after immobilization on gold nanoparticles. The results showed that the complexes supported by tris(2-(6-methyl)pyridyl)methoxymethane (6Me(3)-TPMM) and its thiol-appended ligand displayed faster reactivity. Additionally, the immobilized complexes showed enhanced activity in oxygen-atom transfer reactions (OAT) and hydrogen-atom transfer (HAT) reactions compared to their homogeneous analogues. This study highlights the importance of ligand geometry and immobilization on gold nanoparticles in influencing the reactivity of the complexes.
DALTON TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Rohan Jonnalagadda, Antonio Del Rio Flores, Wenlong Cai, Rimsha Mehmood, Maanasa Narayanamoorthy, Chaoxiang Ren, Jan Paulo T. Zaragoza, Heather J. Kulik, Wenjun Zhang, Catherine L. Drennan
Summary: The isonitrile moiety is essential in marine sponges and some microbes for various processes. Two biosynthetic routes have been identified, involving different sources of nitrogen and carbon atoms. Structural, biochemical, and computational investigations have shed light on the mechanism of isonitrile formation through an unprecedented reaction by the enzyme ScoE.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Clinical Neurology
Haotian Liu, Yong Xie, Xia Wang, Martine Abboud, Chao Ma, Wei Ge, Christopher J. Schofield
Summary: The article discusses the potential roles of 2OGDD in AD, highlighting the relationship with synaptic dysfunction/loss and the importance of regulating neuronal/glial differentiation through enzyme activity-dependent mechanisms to protect against synaptic loss.
ALZHEIMERS & DEMENTIA
(2022)
Article
Multidisciplinary Sciences
Zonghua Ye, Yifeng Wei, Li Jiang, Yan Zhang
Summary: This study reports an alternative mechanism for the oxygenolytic cleavage of sulfoquinovose (SQ) catalyzed by an iron and alpha-ketoglutarate-dependent alkanesulfonate dioxygenase (SqoD, sulfo-ASDO pathway). The marine bacterium Marinomonas ushuaiensis utilizes SQ as a carbon source through the sulfo-ASDO pathway, suggesting potential implications for sulfur recycling in different biological environments.
Article
Multidisciplinary Sciences
David C. Earl, P. Brent Ferrell, Nalin Leelatian, Jordan T. Froese, Benjamin J. Reisman, Jonathan M. Irish, Brian O. Bachmann
NATURE COMMUNICATIONS
(2018)
Article
Biotechnology & Applied Microbiology
Brett C. Covington, Jeffrey M. Spraggins, Audrey E. Ynigez-Gutierrez, Zachary B. Hylton, Brian O. Bachmann
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
C. A. Starbird, Nicole A. Perry, Quyan Chen, Sandra Berndt, Izumi Yamakawa, Lioudmila V. Loukachevitch, Emilianne M. Limbrick, Brian O. Bachmann, T. M. Iverson, Kathryn M. McCulloch
Article
Biochemistry & Molecular Biology
Kathryn M. McCulloch, Izumi Yamakawa, David A. Shifrin, Russell E. McConnell, Nora J. Foegeding, Prashant K. Singh, Suli Mao, Matthew J. Tyska, T. M. Iverson
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Audrey E. Ynigez-Gutierrez, Brian O. Bachmann
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Analytical
Berkley M. Ellis, Caleb N. Fischer, Leroy B. Martin, Brian O. Bachmann, John A. McLean
ANALYTICAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Emilianne M. Limbrick, Audrey E. Ynigez-Gutierrez, Callie C. Dulin, Dagmara K. Derewacz, Jeffrey M. Spraggins, Kathryn M. McCulloch, T. M. Iverson, Brian O. Bachmann
Article
Chemistry, Multidisciplinary
Jacob P. Brannon, Isaac Ramirez, DaShawn Williams, Gregory A. Barding, Yan Liu, Kathryn M. McCulloch, Perumalreddy Chandrasekaran, S. Chantal E. Stieber
JOURNAL OF CHEMICAL EDUCATION
(2020)
Article
Chemistry, Multidisciplinary
Emilianne M. Limbrick, Michael Graf, Dagmara K. Derewacz, Fabian Nguyen, Jeffrey M. Spraggins, Maximiliane Wieland, Audrey E. Ynigez-Gutierrez, Benjamin J. Reisman, Boris Zinshteyn, Kathryn M. McCulloch, T. M. Iverson, Rachel Green, Daniel N. Wilson, Brian O. Bachmann
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Chemistry, Multidisciplinary
Jonathan H. Boyce, Benjamin J. Reisman, Brian O. Bachmann, John A. Porco
Summary: This study reports novel rearrangements of acylphloroglucinols mediated by formic acid to access diverse synthetic acylphloroglucinol scaffolds, with insights on the mechanism provided by Density-functional theory (DFT) analysis. Evaluation of products using multiplexed activity profiling (MAP) identified SASs that suppressed pS6 (Ser235/236) markers of mTOR and ERK signaling pathways activation. These results demonstrate the pharmacological potential of novel chemotypes through biomimetic synthesis and multiplexed activity profiling.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemical Research Methods
Benjamin J. Reisman, Sierra M. Barone, Brian O. Bachmann, Jonathan M. Irish
Summary: Fluorescent cell barcoding (FCB) allows efficient collection of multiple flow cytometry samples, while DebarcodeR provides a computational framework for debarcoding and improvements to experimental methods, significantly enhancing the speed, accuracy, and reproducibility of FCB.
Article
Chemistry, Multidisciplinary
Kathryn M. McCulloch, Katherine A. Hicks
Summary: Second-semester biochemistry students from California State Polytechnic University, Pomona, and the State University of New York College at Cortland collaborated on a semester-long project to produce bioinfographics on metabolic pathways. The project was considered a meaningful capstone project, and the importance of the peer review process in editing the bioinfographics was highlighted.
JOURNAL OF CHEMICAL EDUCATION
(2022)
Article
Chemistry, Organic
Cristina Preston-Herrera, Aaron S. Jackson, Brian O. Bachmann, Jordan T. Froese
Summary: A new periodate-based reactive assay system for fluorescent detection of cis-diol metabolites produced by Rieske dioxygenases has been developed. This sensitive and diastereoselective system effectively evaluates substrate scope and relative activity of a designed Rieske dioxygenase variant library. Its high throughput capacity allows for rapid and efficient substrate scope investigations and screening of large dioxygenase variant libraries.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)