Article
Chemistry, Multidisciplinary
Utumporn Ngivprom, Surayut Kluaiphanngam, Wenjuan Ji, Siriwalee Siriwibool, Anyanee Kamkaew, James R. Ketudat Cairns, Qi Zhang, Rung-Yi Lai
Summary: Nucleocidin 1 is a fluorine-containing natural product, and its biosynthetic gene cluster has been identified, with enzymes nucPNP and NucV playing essential roles. The study reveals the biosynthesis pathway of nucleocidin 1 and the slower catalytic efficiency of NucV compared to its homolog ScAPRT.
Article
Chemistry, Multidisciplinary
Qian Zhang, Hao-Tian Chi, Linrui Wu, Zixin Deng, Yi Yu
Summary: The biosynthesis of apramycin involves phosphorylation, deacetylation, and dephosphorylation steps with the enzymes AprU, AprP, and AprZ. Streptomyces tenebrarius uses C-5 phosphorylation and N-7' acetylation to avoid auto-toxicity of apramycin. This study provides insights for designing new generation AGAs to combat drug-resistant pathogens.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Plant Sciences
Xuan Feng, Qingzhi Zhang, David J. Clarke, Hai Deng, David O'Hagan
Summary: 3'-O-ss-Glucosyl-4',5'-didehydro-5'-deoxyadenosine 13 is a natural product of Streptomyces calvus and Streptomyces virens, and can also be generated in vitro by the enzyme NucGT. Experimental results using oxygen-18 and deuterium isotopes confirm that 13 is not a biosynthetic precursor to nucleocidin 1.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Biochemistry & Molecular Biology
Marta Wojnowska, Xuan Feng, Yawen Chen, Hai Deng, David O'Hagan
Summary: The gene cluster related to the biosynthesis of fluoro- and sulfamyl-metabolite nucleocidin in Streptomyces calvus was investigated through gene knockouts. Most of the deletions did not affect fluorometabolite production, while some specifically abolished sulfamylation or fluorination. Two genes belonging to a phosphoadenosine phosphosulfate (PAPS) gene cluster were found to be essential for sulfamyl assembly. Three genes were essential for fluorination, but their protein product activities are still unknown. These findings provide important genetic information for studying the enzymology of nucleocidin biosynthesis.
Article
Biology
Bing-Bing Ma, Chen-Fan Sun, Jing-Yi Zhou, Shuai-Lei Gu, Xin-Yi Dai, Yan-Zhen Chen, Qing-Wei Zhao, Xu-Ming Mao
Summary: Protein post-translational modifications (PTMs) with various acyl groups in Streptomyces can be further modified, known as post-PTM modification (PPM). By oxidizing the crotonyl groups of an acetyl-CoA synthetase Acs, the protein LimB in Streptomyces roseosporus regulates crotonylation level, morphological development, and antibiotic production.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Doris A. van Bergeijk, Somayah S. Elsayed, Chao Du, Isabel Nunez Santiago, Anna M. Roseboom, Le Zhang, Victor J. Carrion, Herman P. Spaink, Gilles P. van Wezel
Summary: The biosynthetic gene clusters of Actinobacteria are poorly expressed in the laboratory. However, the stress hormone epinephrine has been found to promote their expression and influence the metabolism of Streptomyces. This response is mediated by the catechol moiety.
COMMUNICATIONS CHEMISTRY
(2022)
Article
Biotechnology & Applied Microbiology
Rebecca E. McHugh, John T. Munnoch, Robyn E. Braes, Iain J. W. McKean, Josephine Giard, Andrea Taladriz-Sender, Frederik Peschke, Glenn A. Burley, Andrew J. Roe, Paul A. Hoskisson
Summary: The study revealed that aurodox is a promising antibacterial compound for treating Enterohemorrhagic Escherichia coli (EHEC) infections, targeting the type III secretion system to inhibit infection establishment while avoiding toxin production, providing a basis for future therapeutic developments.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Annalisa Pisciotta, Alessia Maria Sampino, Alessandro Presentato, Marco Galardini, Angel Manteca, Rosa Alduina
Summary: DNA methylation is an epigenetic modification that has been detected in both prokaryotic and eukaryotic genomes. This study focused on the role of cytosine methylation in Streptomyces coelicolor and found that it affects gene expression, growth, and antibiotic biosynthesis. The researchers identified methylated cytosines and methylation motifs in the genome, and demonstrated that cytosine methylation influences gene transcription. This study provides new insights into the role of cytosine methylation in controlling bacterial gene expression.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Physical
Sicong Li, Priscila dos Santos Bury, Fanglu Huang, Junhong Guo, Guo Sun, Anna Reva, Chuan Huang, Xinyun Jian, Yuan Li, Jiahai Zhou, Zixin Deng, Finian J. Leeper, Peter F. Leadlay, Marcio V. B. Dias, Yuhui Sun
Summary: The study reveals the dideoxygenation process of intermediates JI-20A and JI-20B in gentamicin, starting with phosphorylation catalyzed by GenP and then modified by GenB3 and GenB4 to form gentamicin C complex. Insights into the catalytic mechanisms of GenB3 and GenB4 are provided through crystal structures and site-directed mutagenesis.
Article
Chemistry, Multidisciplinary
Xuan Feng, Davide Bello, David O'Hagan
Summary: Three adenosine based metabolites 6-8 were isolated from Streptomyces calvus, structurally related to the fluorine containing antibiotic nucleocidin 1 and glycosylated fluoroadenosines 2 and 3, but lacking fluorine. This suggests that the biosynthetic enzymes for fluorometabolites may also process their non-fluorinated counterparts.
Article
Microbiology
Baral Bikash, Siitonen Vilja, Laughlin Mitchell, Yamada Keith, Ilomaki Mikael, Metsa-Ketela Mikko, Niemi Jarmo
Summary: Streptomyces are efficient chemists in generating diverse chemical scaffolds through secondary metabolism, which is stimulated by interactions with other microbes in their ecosystem. Cultivating Streptomyces with dead yeast cells triggered the production of red pigments through the activation of the cluster-situated regulator mbkZ. The presence of the red cluster in Streptomyces sp. MBK6 illustrates horizontal gene transfer of an entire metabolic pathway and adaptation to a new environment through mutations in the key regulatory protein MbkZ's receiver domain.
FEMS MICROBIOLOGY LETTERS
(2021)
Article
Biotechnology & Applied Microbiology
Jun Luo, Dong Yang, Hindra, Ajeeth Adhikari, Liao-Bin Dong, Fei Ye, Xiaohui Yan, Christoph Rader, Ben Shen
Summary: The discovery of a new sub-family of AMM congeners, named AMEs, with different chemical features and modest cytotoxicity against cancer cells, expands the understanding of structure-activity relationship for pyrroloquinoline alkaloids. Comparative analysis of the gene clusters of AMEs and AMMs supports the use of a scaffold peptide for biosynthesis of the pyrroloquinoline family of natural products, providing insights for future efforts in mimicking Nature's combinatorial biosynthetic strategies for natural product structural diversity.
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
(2021)
Article
Microbiology
Bartosz Bednarz, Aaron Millan-Oropeza, Magdalena Kotowska, Michal swiat, Juan J. Quispe Haro, Celine Henry, Krzysztof Pawlik
Summary: This study investigated the impact of SARP family regulators on the synthesis of specialized metabolites in Streptomyces, finding that cpkO and cpkN are crucial for coelimycin synthesis and are regulated by the quorum sensing molecule ScbR.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Yuchen Li, Seoung Rak Lee, Esther J. Han, Mohammad R. Seyedsayamdost
Summary: Natural products are important sources of pharmaceuticals and chemical tools. This study focused on the discovery of new natural products from well-studied strains, specifically targeting Streptomyces rimosus, a widely-used oxytetracycline producer. Through MALDI-MS-guided high-throughput elicitor screening (HiTES), the researchers mapped the metabolome of S. rimosus and characterized three cryptic biosynthetic gene clusters, including the unusual cyclic peptide natural product momomycin. The study demonstrated that HiTES is an effective approach for finding new chemical matter from drained strains.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Huan Liu, Jie Fan, Peng Zhang, Youcai Hu, Xingzhong Liu, Shu-Ming Li, Wen-Bing Yin
Summary: By genome mining and gene deletion approaches in fungi, a new enzyme TdaR was discovered to catalyze the formation of unique disulfide bridges in various organic molecules.
Article
Chemistry, Organic
Manuele Musolino, Ian N. Fleming, Lutz F. Schweiger, David O'Hagan, Sergio Dall'Angelo, Matteo Zanda
Summary: The synthesis of five radiotracers with different oxyamine spacers between the hypoxia-reactive 2-nitroimidazole moiety and the 5-[F-18]-fluorodeoxyribose prosthetic group was reported. Among them, tracer 15 d displayed superior uptake kinetics and similar selectivity for hypoxic cells compared to standard hypoxia tracers. Lipophilicity and structural rigidity significantly influenced the selectivity of the tracers towards hypoxic cells.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Editorial Material
Chemistry, Organic
David O'Hagan
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Crystallography
Shigeyuki Yamada, Yizhou Wang, Masato Morita, Qingzhi Zhang, David O'Hagan, Masakazu Nagata, Tomohiro Agou, Hiroki Fukumoto, Toshio Kubota, Mitsuo Hara, Tsutomu Konno
Summary: Photoluminescent liquid crystals (PLLCs) have attracted attention for their broad applicability in thermosensing and PL switching. By developing bistolane derivatives with alkyl or fluoroalkyl flexible chains, the study showed that fluoroalkyl-containing bistolanes exhibit stronger deep blue PL than their non-fluorinated counterparts, even in the crystalline phase, due to the construction of rigid molecular aggregates to suppress non-radiative deactivation.
Article
Biotechnology & Applied Microbiology
Tiia Kittila, Patricia Calero, Folmer Fredslund, Phillip T. Lowe, David Teze, Manuel Nieto-Dominguez, David O'Hagan, Pablo Nikel, Ditte H. Welner
Summary: This study explores the effect of oligomerization status on the catalytic properties of fluorinase and reveals that hexamerization is not necessary for fluorination activity. Oligomerization has a long-range effect on substrate binding, decreasing substrate dissociation and release. In addition, the practical application of trimeric fluorinase in in vitro fluorometabolite synthesis is demonstrated.
MICROBIAL BIOTECHNOLOGY
(2022)
Article
Chemistry, Organic
Mengfan He, Weihong Liu, Chen Zhang, Yingjian Liu, Hanyi Zhuang, David O'Hagan
Summary: C-2 fluorinated and methylated stereoisomers of citronellol 1 and its oxalate esters, prepared from (R)-pulegone 11, were found to be agonists of human olfactory receptor OR1A1. Isomer preferences were observed, with C-2 difluorination being the most active compound.
Article
Biochemistry & Molecular Biology
Marta Wojnowska, Xuan Feng, Yawen Chen, Hai Deng, David O'Hagan
Summary: The gene cluster related to the biosynthesis of fluoro- and sulfamyl-metabolite nucleocidin in Streptomyces calvus was investigated through gene knockouts. Most of the deletions did not affect fluorometabolite production, while some specifically abolished sulfamylation or fluorination. Two genes belonging to a phosphoadenosine phosphosulfate (PAPS) gene cluster were found to be essential for sulfamyl assembly. Three genes were essential for fluorination, but their protein product activities are still unknown. These findings provide important genetic information for studying the enzymology of nucleocidin biosynthesis.
Article
Chemistry, Multidisciplinary
Zeguo Fang, Cihang Yu, Michael Buhl, David O'Hagan
Summary: Stimulated by a suggestion, deuterated isotopologues of cycloalkanes were prepared to investigate their polarity. The results showed that the Deuterium-labeled hexafluorocyclohexane is not more polar than its protio form, while deuterated cyclopentane may indeed be slightly more polar than the unlabeled compound. The retention time analysis also indicated the increased polarity associated with perdeuteration.
HELVETICA CHIMICA ACTA
(2023)
Article
Chemistry, Physical
Bruno A. Piscelli, David O'Hagan, Rodrigo A. Cormanich
Summary: The importance of electrostatic nonconventional hydrogen bonds (NCHBs) for the pseudo-anomeric effect of 4-substituted methoxycyclohexanes was evaluated using theory. By deconvoluting electrostatic effects from other contributing effects, it was found that there is an interesting interplay between sigma CH -> sigma CX* hyperconjugation and the electropositive charge on 3,5-axial hydrogens (Hax). Better sigma CX* (or pi CO*) acceptors increase the charge on 3,5-CHax, which in turn strengthens C delta+Hax center dot center dot center dot delta-OMeNCHB interactions.
JOURNAL OF PHYSICAL CHEMISTRY A
(2023)
Editorial Material
Chemistry, Medicinal
David O'Hagan, Robert J. Young
MEDICINAL CHEMISTRY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Oluwayinka O. Oke, Yawen Chen, Chukwuemeka Isanbor, Olayinka T. Asekun, David O'Hagan
Summary: This paper describes efficient conversion methods of fluorinated and trifluoromethyl-substituted benzoic acids to benzamides using the soil bacteria Streptomyces sp. JCM9888, as well as the efficient reduction of the same substrates to benzyl alcohols using the fungus Cunninghamella elegans. These biotransformations show surprising efficiency and may have disruptive potential in process chemistry.
BIOCATALYSIS AND BIOTRANSFORMATION
(2023)
Article
Chemistry, Medicinal
Yohann J. G. Renault, Jiayin Diao, David B. Cordes, Katie Leach, David O'Hagan
Summary: This article presents a synthetic route that combines MacMillan organocatalytic asymmetric a-fluorination and reductive amination to access bioactive beta-fluoroamines. The method is demonstrated through the synthesis of (S)-3-fluoro-gamma-aminobutyric acid (3F-GABA) and the stereoisomers of beta-fluoroamines of cinacalcet, tecalcet, fendiline, and NPS R-467. The binding preference of the stereoisomers to the calcium receptor (CaR) was assessed through a CaR receptor assay, which revealed conformations favored by the electrostatic gauche effect.
MEDICINAL CHEMISTRY RESEARCH
(2023)
Article
Chemistry, Physical
Christian Fischer, Saunak Das, Qingzhi Zhang, Yangbiao Liu, Lothar Weinhardt, David O'Hagan, Michael Zharnikov, Andreas Terfort
Summary: We report on the effects of integrating PFCH groups into self-assembled monolayers on Au(111). These new monolayers have lower packing density and unique orientation structures, resulting in lower water contact angles and moderate work function values compared to other partly fluorinated monolayers. Despite the lower packing density, the interaction between terminal PFCH moieties enhances the stability of these monolayers towards potential molecular substituents.
Article
Chemistry, Multidisciplinary
Cihang Yu, Bruno A. Piscelli, Nawaf Al Maharik, David B. Cordes, Alexandra M. Z. Slawin, Rodrigo A. Cormanich, David O'Hagan
Summary: Theory and solution NMR studies have shown that the expected tri-equatorial conformation is adopted by all-syn 1,3,5-trifluorocyclohexane 5. However, in the solid state, a more polar triaxial conformation is observed. This study investigates the preferred conformations of substituted derivatives of 5 (Me, OMe, NH(CO)Me, NHBoc) to gain insight into the triaxial C-F preferences.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Thomas J. Poskin, Bruno A. Piscelli, Keigo Yoshida, David B. Cordes, Alexandra M. Z. Slawin, Rodrigo A. Cormanich, Shigeyuki Yamada, David O'Hagan
Summary: Concise and general synthesis protocols are reported for the generation of mono-, di-, and tri-alkylated cyclohexanes with a single fluorine atom located on the remaining carbons of the ring. The alkyl groups are positioned equatorially and possess triaxial C-F bonds, which introduce polarity to these ring systems. Intermolecular electrostatic interactions in the solid-state structure of the trialkylated systems are investigated, and the resulting supramolecular order presents potential for design in soft materials.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Yawen Chen, Qingzhi Zhang, Xuan Feng, Marta Wojnowska, David O'Hagan
Summary: Genome homology and the presence of a putative biosynthetic gene cluster led to the identification of Streptomyces aureorectus DSM 41692 and Streptomyces virens DSM 41465 as candidate producers of the antibiotic nucleocidin 1. When cultured in medium supplemented with fluoride, these bacterial strains produced nucleocidin 1 along with other compounds, including 4'-fluoro-3'-O-beta-glucosylated adenosine 2.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Organic
Faiza Diaba, Gisela Trenchs
Summary: The first violet light-mediated synthesis of gamma- and delta-lactams from N-alkenyl trichloroacetamides is reported in this paper. The reactions are conducted in tetrahydrofuran or 2-methyltetrahydrofuran as the sole solvent without catalysts or additives, under non-anhydrous conditions in an air atmosphere where the solvent serves as the radical initiator.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Feroze Hussain, Sajjad Ahmed, Ashiq Hussain Padder, Qazi Naveed Ahmed
Summary: This study reports a novel and efficient one-pot synthesis method for mixed phosphorotrithioates, which does not require supplementary additives and shows broad applicability.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Hyunjin Oh, Ikyon Kim
Summary: A new 1,2,4-triazole-pyrrolo[1,2-a]pyrazine hybrid system, 6-acylpyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, was synthesized using a catalyst-free method. This method involved sequential exposure of pyrrole-2-carbonitrile-derived substrates to DMF-DMA and acyl hydrazide, resulting in the formation of acylated pyrazine and 1,2,4-triazole rings, enabling the installation of various substituents at specific positions on the core skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Ming Yan, Si-fan Wang, Yong-po Zhang, Jin-zhong Zhao, Zhuo Tang, Guang-xun Li
Summary: Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. The reaction allows for the gram-scale preparation of sulfinamides and the one-pot synthesis of various sulfonyl amides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Farzaneh Bandehali-Naeini, Zahra Tanbakouchian, Noushin Farajinia-Lehi, Nicolas Mayer, Morteza Shiri, Martin Breugst
Summary: Two tandem catalytic systems were developed for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts. Different maleimide structures can be synthesized using either Pd or Cu catalysis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Tanya Raghava, Anjan Chattopadhyay, Subhadeep Banerjee, Nivedita Sarkar
Summary: Amine substitution of two ortho fluorine atoms of tetrafluoroterephthalonitrile through SNAr chemistry is easily achievable. But further fluorine substitution is only possible under forcing conditions, yielding valuable fluorophores for bioimaging.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Review
Chemistry, Organic
Anju Chadha, Santosh Kumar Padhi, Selvaraj Stella, Sowmyalakshmi Venkataraman, Thangavelu Saravanan
Summary: Alcohol dehydrogenases are enzymes that use cofactors for oxidation or reduction reactions of alcohols or carbonyl compounds. They are utilized in green chemistry and have applications in the production of pharmaceuticals. Recombinant enzymes have solved the challenge of producing purified enzymes in large quantities. Engineered alcohol dehydrogenases have been used in asymmetric synthesis in industry. Various methods have been established for regenerating expensive cofactors to make the enzymatic process more efficient and economically viable.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
