Review
Biotechnology & Applied Microbiology
Dani Permana, Takuya Kitaoka, Hirofumi Ichinose
Summary: Cytochrome P450s are heme-containing monooxygenases found in all biological kingdoms. Fungi, in particular, are an important source of diverse P450s that play key roles in sterol synthesis. This review discusses fungal P450s and their applications in bioconversion and biosynthesis, highlighting their history, availability, and versatility. The ability of P450s to catalyze various reactions makes them promising enzymes for numerous applications, and future research in this field is encouraged.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Chemistry, Inorganic & Nuclear
Nidhi Awasthi, Rolly Yadav, Anamika Shukla, Devesh Kumar
Summary: This study investigates the hydroxylation of 4-nitrophenol by Cytochrome P450 metalloenzyme, revealing a single state reactivity pathway.
INORGANIC CHEMISTRY COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Qian Wei, Ze-Ping Wang, Xiao Zhang, Yi Zou
Summary: This study reports a novel strategy for enzymatic diaryl ether generation through a nonoxidative manner. A versatile thioesterase domain was discovered to catalyze the formation of diarly ethers and insights into its catalytic process were provided through further mutations and biochemical analyses.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Justin C. Miller, Mary A. Schuler
Summary: This study identified key residues that toggle SLS and SLAS selectivity in two CYP72A subfamily enzymes from Camptotheca acuminata. The mutations in substrate recognition sequence 1 (SRS1) determine the selectivity, and changes in other regions can also affect enzyme activity towards different substrates. Understanding the determinants of selectivity in these enzymes provides opportunities for more tailored heterologous production of TIAs.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Plant Sciences
Akiyoshi Yoda, Xiaonan Xie, Kaori Yoneyama, Kenji Miura, Christopher S. P. McErlean, Takahito Nomura
Summary: Seeds of root parasitic plants are induced to germinate by strigolactones exudated from host roots. The biosynthesis pathway of 5-deoxystrigol, a major strigolactone, has not been fully understood. In this study, researchers identified Sobic.005G213500 as a regulator that affects the stereoselective biosynthesis of 5-deoxystrigol and provides insights into how different strigolactones are produced to combat parasitic weed infestations.
PLANT AND CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lemeng Dong, Aldo Almeida, Jacob Pollier, Bekzod Khakimov, Jean-Etienne Bassard, Karel Miettinen, Dan Staerk, Rahimi Mehran, Carl Erik Olsen, Mohammed Saddik Motawia, Alain Goossens, Soren Bak
Summary: Through de novo transcriptomics and comparative genomics, researchers revealed the evolutionary origin of the insect deterrent cucurbitacins in Iberis amara, identifying key enzymes and catalytic steps in cucurbitacin biosynthesis. Additionally, the results showed that cucurbitacin biosynthesis has evolved convergently in different plant families through different biosynthetic routes. This study provides new insights into the mechanism of recurrent evolution and diversification of plant defensive chemicals.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Biotechnology & Applied Microbiology
Bashu Dev Pardhe, Kyoung Pyo Kwon, Jong Kook Park, Jun Hyuck Lee, Tae-Jin Oh
Summary: In this study, CYP105D18 was used as a catalyst for the hydroxylation of steroids with H2O2 as a co-substrate. The hydroxylation positions of different steroids were predicted based on experimental data and molecular docking. Mutations in the substrate access channel were performed to improve substrate conversion. The findings provide a basis for the potential application and further engineering of CYP105D18.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2023)
Article
Plant Sciences
Akiyoshi Yoda, Narumi Mori, Kohki Akiyama, Mayu Kikuchi, Xiaonan Xie, Kenji Miura, Kaori Yoneyama, Kanna Sato-Izawa, Shinjiro Yamaguchi, Koichi Yoneyama, David C. Nelson, Takahito Nomura
Summary: The LGS1 gene in sorghum is involved in the synthesis of substances that affect seed germination in root parasitic plants, proposing a novel SL biosynthetic pathway involving sulfo group catalysis and cyclization of 18-OH-CLA.
Article
Plant Sciences
Andrew Muchlinski, Meirong Jia, Kira Tiedge, Jason S. Fell, Kyle A. Pelot, Lisl Chew, Danielle Davisson, Yuxuan Chen, Justin Siegel, John T. Lovell, Philipp Zerbe
Summary: This study reports the discovery of five cytochrome P450 monooxygenases in switchgrass, forming previously unknown furanoditerpenoids. Combinatorial pathway reconstruction showed that these enzymes catalyze furan ring addition directly. Transcriptional co-expression patterns and the presence of specific diterpenoids in roots support the occurrence of P450-derived furanoditerpenoids in planta.
Article
Plant Sciences
Shu-Ming Li, Zheng-Xi Zhang, Zhang-Hai Li
Summary: The highly oxygenated indole alkaloid speradine F (4) with a 6/5/6/5/5/5 hexacyclic skeleton was isolated from a culture of Penicillium palitans, together with its precursors beta-cyclopiazonic acid (beta-CPA, 5) and cyclopiazonic acid (CPA, 1). Gene deletion and heterologous expression led to the identification of the responsible five-gene spe cluster for the speradine skeleton formation. Precursor supply experiments proved that 1 was enzymatically converted, via 2-oxoCPA (2), to speradine A (3), which subsequently undergoes multistep nonenzymatic hydroxylations to 4.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Multidisciplinary
Yan-Long Yang, Man Zhou, Lin Yang, Markus Gressler, Johannes Rassbach, Jacob M. Wurlitzer, Ying Zeng, Kun Gao, Dirk Hoffmeister
Summary: In this study, the genetic locus responsible for the biosynthesis of panepoxydone in the basidiomycete mushroom Panus rudis was identified. The cytochrome P450 enzyme PanH was characterized as the catalyst for epoxide formation in this pathway. The study also demonstrated the ability to synthesize bioactive epoxycyclohexenone compounds using a PanH-producing yeast as a biocatalyst.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Chunshun Li, Yifei Hu, Xiaohua Wu, Spencer D. Stumpf, Yunci Qi, John M. D'Alessandro, Keshav K. Nepal, Ariel M. Sarotti, Shugeng Cao, Joshua A. V. Blodgett
Summary: Rare actinomycetes are a valuable but underexploited source of bioactive compounds. In this study, a targeted metabologenomic approach was used to identify piperazyl compounds in the rare actinomycete Lentzea flaviverrucosa DSM 44664. The discovery of two dimeric biaryl-cyclohexapeptides, petrichorins A and B, with potent anticancer activity, highlights the potential of rare actinomycetes for drug discovery.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Andrew J. J. Devine, Alice E. E. Parnell, Catherine R. R. Back, Nicholas R. R. Lees, Samuel T. T. Johns, Ainul Z. Z. Zulkepli, Rob Barringer, Katja Zorn, James E. M. Stach, Matthew P. P. Crump, Martin A. A. Hayes, Marc W. W. van der Kamp, Paul R. R. Race, Christine L. L. Willis
Summary: This study reveals the key epoxidation reaction in the synthesis of Abyssomicin C and the structure of the enzyme AbyV involved in this reaction. The combination of selective carbon-13 labeling with NMR spectroscopy proves to be an important tool in studying enzyme-catalyzed reactions in vitro.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Chao Shi, Mingyue Gu, Zhangxin Chen, Xiaonan Huang, Juan Guo, Luqi Huang, Jie Deng, Ke He, Lei Zhang, Lixin Huang, Zhenzhan Chang
Summary: The study revealed the crystal structures of CYP76AH1 and its natural substrate miltiradiene, providing important insights into its catalytic mechanism and the basis for improving tanshinone production.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
E. O. Yablokov, T. A. Sushko, L. A. Kaluzhskiy, A. A. Kavaleuski, Y. Mezentsev, P. Ershov, A. A. Gilep, A. S. Ivanov, N. Strushkevich
Summary: The study demonstrates that steroid substrates have different effects on the affinity and stability of CYP11s-Adx complexes, with cholesterol increasing the formation rate of CYP11A1 - Adx complex and decreasing the stability of CYP11B1 - Adx and CYP11B2 - Adx complexes. This differentiation in protein-protein interactions within the mitochondrial pool of CYPs reveals the potential impact of substrate regulation on overall steroid hormones production. The experimental data provide further insights into the redox chains involved in steroidogenesis.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Article
Microbiology
Jennifer F. Carr, Hannah J. Lee, Joshua B. Jaspers, Albert E. Dahlberg, Gerwald Jogl, Steven T. Gregory
JOURNAL OF BACTERIOLOGY
(2015)
Article
Genetics & Heredity
Guray Kuzu, Emily G. Kaye, Jessica Chery, Trevor Siggers, Lin Yang, Jason R. Dobson, Sonia Boor, Jacob Bliss, Wei Liu, Gerwald Jogl, Remo Rohs, Nadia D. Singh, Martha L. Bulyk, Michael Y. Tolstorukov, Erica Larschan
Article
Microbiology
Hasan Demirci, Frank V. Murphy, Eileen L. Murphy, Jacqueline L. Connetti, Albert E. Dahlberg, Gerwald Jogl, Steven T. Gregory
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2014)
Article
Microbiology
Steven T. Gregory, Jacqueline L. Connetti, Jennifer F. Carr, Gerwald Jogl, Albert E. Dahlberg
JOURNAL OF BACTERIOLOGY
(2014)
Article
Biochemistry & Molecular Biology
Hua Li, Gerwald Jogl
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2013)
Article
Biochemistry & Molecular Biology
Hasan Demirci, Leyi Wang, Frank V. Murphy, Eileen L. Murphy, Jennifer F. Carr, Scott C. Blanchard, Gerwald Jogl, Albert E. Dahlberg, Steven T. Gregory
Article
Chemistry, Multidisciplinary
Kyle W. East, Jocelyn C. Newton, Uriel N. Morzan, Yogesh B. Narkhede, Atanu Acharya, Erin Skeens, Gerwald Jogl, Victor S. Batista, Giulia Palermo, George P. Lisi
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Infectious Diseases
Erin E. Killeavy, Gerwald Jogl, Steven T. Gregory
Article
Multidisciplinary Sciences
Eileen L. Murphy, Kavindra V. Singh, Bryant Avila, Torsten Kleffmann, Steven T. Gregory, Barbara E. Murray, Kurt L. Krause, Reza Khayat, Gerwald Jogl
SCIENTIFIC REPORTS
(2020)
Article
Infectious Diseases
Yan Chen, Yanqin Tu, Tingyu Pan, Zixin Deng, Lian Duan
Summary: Dithiolopyrrolone antibiotics have well-known biological activities, but the biosynthesis mechanism of the characteristic bicyclic scaffold is still unknown. In this study, the adenylation domain of a multi-domain non-ribosomal peptide synthase DtpB from the biosynthetic gene cluster of thiolutin was found to not only recognize and adenylate cysteine, but also play a crucial role in peptide bond formation. Additionally, an eight-membered ring compound was discovered as an intermediate during the formation of the bicyclic structure. These findings propose a new biosynthesis mechanism for the bicyclic scaffold of dithiolopyrrolones and reveal additional functions of the adenylation domain.
Meeting Abstract
Chemistry, Multidisciplinary
Jocelyn C. Newton, Gerwald Jogl, John M. Sedivy
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2018)
Article
Biochemistry & Molecular Biology
Patrick N. Blank, Golda H. Barrow, Wayne K. W. Chou, Lian Duan, David E. Cane, David W. Christianson
Article
Biochemistry & Molecular Biology
Travis A. Pemberton, Mengbin Chen, Golda G. Harris, Wayne K. W. Chou, Lian Duan, Mustafa Koksal, Alex S. Genshaft, David E. Cane, David W. Christianson