Article
Multidisciplinary Sciences
Britta Frensch, Thorsten Lechtenberg, Michel Kather, Zeynep Yunt, Martin Betschart, Bernd Kammerer, Steffen Luedeke, Michael Mueller, Joern Piel, Robin Teufel
Summary: The study uncovers the enzymatic formation process of the spiroketal moiety in rubromycin polyketides, driven by flavin-dependent enzymes, and characterizes reaction intermediates.
NATURE COMMUNICATIONS
(2021)
Review
Chemistry, Multidisciplinary
Sandeep Pimparkar, Adithyaraj Koodan, Siddhartha Maiti, Nesreen S. Ahmed, Mohamed Mokhtar M. Mostafa, Debabrata Maiti
Summary: Nitrile or cyano compounds play vital roles in various fields such as dyes, agrochemicals, medicinal compounds, and electronic materials. Aryl nitrile serves as an important intermediate in the preparation of numerous compounds through different transformation processes. Over the past decades, diverse cyanation methods have been developed, facilitating the introduction of sensitive functional groups and serving as essential tools in the synthesis of natural products and medicinal compounds.
CHEMICAL COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Guiyun Zhao, Wei Peng, Kaihui Song, Jingkun Shi, Xingyu Lu, Binju Wang, Yi-Ling Du
Summary: A study on a class of di-domain enzymes in hydrazine bond formation revealed key steps involved in N-N bond formation, which may aid in the development of novel enzyme catalysts in the future.
NATURE COMMUNICATIONS
(2021)
Review
Biotechnology & Applied Microbiology
Richiro Ushimaru, Jiaqi Lyu, Ikuro Abe
Summary: Tetrapyrroles are a unique class of natural products with diverse chemical structures and broad biological functions. They play essential roles as enzyme cofactors and certain metal-free porphyrin metabolites may have beneficial activities for both organisms and humans. The unique properties of tetrapyrrole natural products come from their extensively modified and conjugated macrocyclic core structures. The biosynthesis of most tetrapyrroles starts from a precursor molecule called uroporphyrinogen III, which contains propionate and acetate side chains. Several modification enzymes and catalytic activities have been identified for cleavage of the propionate side chains from the macrocycles.
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Hannah. A. A. Minas, Romain M. M. Francois, Franziska Hemmerling, Amy. E. E. Fraley, Cora. L. L. Dieterich, Simon. H. H. Ruedisser, Roy. A. A. Meoded, Sabrina Collin, Kira. J. J. Weissman, Arnaud Gruez, Jorn Piel
Summary: Modular trans-acyltransferase polyketide synthases (trans-AT PKSs) are enzymatic assembly lines that introduce remarkable chemical diversity into their polyketide products. This study focuses on the lobatamide A PKS, which incorporates a methylated oxime. By analyzing the structure and mutagenesis of the oxygenase, the authors propose a catalysis model and identify key protein-protein interactions. This work expands the biomolecular toolbox for trans-AT PKS engineering and enables the introduction of masked aldehyde functionalities into diverse polyketides.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Hui Xia, Jinsong Song, Changfan Li, Feng Xue
Summary: Biocatalytic promiscuity, a rapidly developing field in biochemistry, offers an alternative strategy for the formation of C-N bonds, which are crucial for the production of various pharmaceuticals and agrochemicals. This review focuses on recent progress in utilizing promiscuous enzymes for constructing C-N bonds.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Eveline Vriens, Dries De Ruysscher, Angus N. M. Weir, Sofie Dekimpe, Gert Steurs, Ahmed Shemy, Leentje Persoons, Ana Rita Santos, Christopher Williams, Dirk Daelemans, Matthew P. Crump, Arnout Voet, Wim De Borggraeve, Eveline Lescrinier, Joleen Masschelein
Summary: In this study, the oximidine gene cluster was identified in Pseudomonas baetica, and four novel oximidine variants were characterized, including a structurally simpler intermediate. Through a combination of in vivo, in vitro, and computational approaches, the biosynthetic pathway of oximidine and an unprecedented mechanism for O-methyloxime formation were experimentally elucidated, expanding the catalytic capabilities of trans-AT PKSs and identifying potential strategies for the production of novel oximidine analogues.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemical Research Methods
Xuechen Zhu, Vilja Siitonen, Charles E. Melancon, Mikko Metsa-Ketela
Summary: Synthetic biology-based approaches were employed to construct five biosynthetic pathways in Streptomyces coelicolor M1152, resulting in the production of four distinct PK-II core structures, offering the opportunity for further controlled production of diverse PK-IIs in a heterologous host.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Qingpei Liu, Dan Zhang, Shuaibiao Gao, Xianhua Cai, Ming Yao, Yao Xu, Yifu Gong, Ke Zheng, Yigui Mao, Liyan Yang, Dengfeng Yang, Istvan Molnar, Xiaolong Yang
Summary: It was found that Orsellinic acid (OA) derivatives are synthesized by filamentous fungi using nonreducing polyketide synthases (nrPKSs). The chain-releasing thioesterase (TE) domains of such nrPKSs were proposed to also catalyze dimerization to yield didepsides, such as lecanoric acid. Through combinatorial domain exchanges, domain dissections and reconstitutions, it was revealed that the TE domain of the lecanoric acid synthase Preu6 of Preussia isomera must collaborate with the starter acyl transferase (SAT) domain from the same nrPKS. Artificial SAT-TE fusion proteins were shown to be highly effective catalysts and able to reprogram the ketide homologation chassis to form didepsides. The dissected SAT and TE domains of Preu6 were also demonstrated to physically interact, indicating the potential co-evolution of SAT and TE domains in OA-synthesizing nrPKSs. This study highlights an unexpected domain-domain interaction in nrPKSs and its significance in the biosynthesis of unnatural didepsides, depsidones, and diphenyl ethers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Yu Meng Yang, Er Juan Zhao, Wanqing Wei, Zi Fei Xu, Jing Shi, Xuan Wu, Bo Zhang, Yasuhiro Igarashi, Rui Hua Jiao, Yong Liang, Ren Xiang Tan, Hui Ming Ge
Summary: In this study, a cytochrome P450 enzyme that can catalyze the formation of a benzene ring from an acyclic polyene substrate has been characterized. Through genome mining guided by this P450 enzyme, 12 homologous type I polyketide synthase gene clusters were obtained, among which two clusters were found to produce trialkyl-substituted aromatic polyketides. Quantum chemical calculations were performed to explore the possible mechanism for the P450-catalyzed benzene ring formation, expanding our knowledge of the catalytic diversity of cytochrome P450.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(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
Microbiology
Elena Forchielli, Daniel Sher, Daniel Segre
Summary: Microbial communities play a critical role in carbon cycling in marine environments. However, current models fail to capture the metabolic heterogeneity of heterotrophic bacteria, which are important for the modification of organic matter. In this study, we characterized the carbon source utilization preferences of 63 marine bacteria and found that their metabolic preferences are strongly predicted by key enzymes belonging to enriched metabolic pathways. The availability of systematic phenotypes can facilitate future modeling efforts and studies of interspecies interactions.
Article
Chemistry, Physical
Qiu-Yue Nie, Zhen-Yu Ji, Yu Hu, Gong-Li Tang
Summary: Two reductases (TjhO5 and TjhD4) were identified to highly reduce the alpha,beta-unsaturated ketone of the D-ring in unconventional tetracyclines, completing the entire transformation via two distinct pathways involving different enzymatic mechanisms. TjhO5-mediated continuous reduction of C = O to CH2 possibly involved a distinctive deoxygenation mechanism. These findings highlight the unusual post-modification of tetracyclines and facilitate further engineering and biocatalysis to enrich the structural diversities.
Article
Chemistry, Multidisciplinary
Friedrich J. Ehinger, Sarah P. Niehs, Benjamin Dose, Maria Dell, Jana Krabbe, Sacha J. Pidot, Timothy P. Stinear, Kirstin Scherlach, Claudia Ross, Gerald Lackner, Christian Hertweck
Summary: The biosynthesis of the hepatotoxic cyclopeptides Rhizonin A and B has been elucidated, revealing the role of Mycetohabitans endofungorum in producing the key component 3-furylalanine (Fua). Genome sequencing and gene inactivation experiments identified the gene cluster responsible for Rhizonin biosynthesis and isotope labeling experiments confirmed the precursor of Fua. Further analysis revealed a novel enzyme RhzB that catalyzes Fua formation and led to the discovery of the bingchamide biosynthesis gene cluster.
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 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, Medicinal
Hiroko Kobayashi, Ryo Suzuki, Kei Sato, Takatoshi Ogami, Hiroshi Tomozawa, Masahito Tsubata, Koji Ichinose, Masaki Aburada, Wataru Ochiai, Kiyoshi Sugiyama, Tsutomu Shimada
JOURNAL OF NATURAL MEDICINES
(2018)
Review
Food Science & Technology
Susumu Okamoto, Hiromi Kameya
JOURNAL OF THE JAPANESE SOCIETY FOR FOOD SCIENCE AND TECHNOLOGY-NIPPON SHOKUHIN KAGAKU KOGAKU KAISHI
(2018)
Article
Biochemistry & Molecular Biology
Vilja Siitonen, Benjamin Nji Wandi, Akke-Pekka Tormanen, Mikko Metsa-Ketela
ACS CHEMICAL BIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Thadee Grocholski, Keith Yamada, Jari Sinkkonen, Heli Tirkkonen, Jarmo Niemi, Mikko Metsa-Ketela
ACS CHEMICAL BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Makoto Hashimoto, Takaaki Taguchi, Kazuki Ishikawa, Ryuichiro Mori, Akari Hotta, Susumu Watari, Kazuaki Katakawa, Takuya Kumamoto, Susumu Okamoto, Koji Ichinose
Article
Multidisciplinary Sciences
Yoshihisa Wakita, Asako Saiki, Hirotaka Kaneda, Shuichi Segawa, Youichi Tsuchiya, Hiromi Kameya, Susumu Okamoto
SCIENTIFIC REPORTS
(2019)
Article
Biochemistry & Molecular Biology
Xiaofeng Cai, Takaaki Taguchi, Huili Wang, Megumi Yuki, Megumi Tanaka, Kai Gong, Jinghua Xu, Yiming Zhao, Koji Ichinose, Aiying Li
Summary: A new C-glycosyltransferase Med-8 is essential for the biosynthesis of medermycin, recognizing a rare deoxyaminosugar. Genes involved in the biosynthesis of angolosamine were proven functional for C-glycosylation. A C-glycosylation cassette composed of these genes could convert a proposed substrate into a C-glycosylated product.
ACS CHEMICAL BIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Xiaofeng Cai, Caiyun Li, Koji Ichinose, Yali Jiang, Ming Liu, Huili Wang, Caixia Gong, Le Li, Juan Wan, Yiming Zhao, Qing Yang, Aiying Li
Summary: Med-ORF10, a single-domain protein of unknown function, plays a regulatory role in medermycin biosynthesis pathway by controlling the expression of genes encoding tailoring enzymes. Its overexpression leads to increased medermycin production and has pleiotropic effects on more targets. However, it is suggested that Med-ORF10 regulates medermycin biosynthesis indirectly, as no direct interaction with target promoter DNA was detected.
MICROBIAL BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Takuya Kumamoto, Mika Kainuma, Azusa Takahashi, Yoshika Matsuo, Kazuaki Katakawa, Takaaki Taguchi, Koji Ichinose
Summary: This article reports the total synthesis of 6-deoxydihydrokalafungin (DDHK) and its epimer, epi-DDHK, as well as a semisynthetic approach from (S)-DNPA. Different reaction sequences were used to successfully obtain these two compounds.
Article
Biochemistry & Molecular Biology
Kazuki Ishikawa, Masaki Ishii, Takashi Yaguchi, Toshiaki Katada, Koji Ichinose, Shinya Ohata
Summary: The nuclear factor-kappa B (NF-kappa B) signaling pathway plays a crucial role in inflammatory responses and cancer pathogenesis. In this study, the alkaloid aszonalenin and its analog epi-aszonalenin B were identified as inhibitors of NF-kappa B activity, making them potential therapeutic compounds for supratentorial ependymomas (ST-EPN-RELA).
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Kazuki Ishikawa, Makoto Hashimoto, Kunpei Komatsu, Takaaki Taguchi, Susumu Okamoto, Koji Ichinose
Summary: Actinorhodin (ACT) is an antibiotic produced by Streptomyces coelicolor A3(2), which has been widely studied as a model organism for antibiotic biosynthesis and regulation. The study found that ActVI-ORF2 is a stereospecific enoyl reductase that converts (S)-DNPA to DDHK.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Makoto Hashimoto, Susumu Watari, Takaaki Taguchi, Kazuki Ishikawa, Takuya Kumamoto, Susumu Okamoto, Koji Ichinose
Summary: In this study, we identified two enzymes, ActVA-ORF4 and ActVA-ORF3, involved in the last step of ACT biosynthesis. ActVA-ORF4 catalyzes the intermolecular C-C bond formation using DHK-OH as the substrate, while ActVA-ORF3 is a quinone-forming enzyme that produces the coupling substrate DHK-OH and the final product ACT.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Food Science & Technology
Hiromi Kameya, Mika Kanazaki, Susumu Okamoto
FOOD SCIENCE AND TECHNOLOGY RESEARCH
(2019)
Review
Biotechnology & Applied Microbiology
Bikash Baral, Amir Akhgari, Mikko Metsa-Ketela
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2018)
