Article
Biochemistry & Molecular Biology
Young-Jin Son, Hee-Jong Hwang, Yonghoon Kwon
Summary: This study reports the scalable biosynthesis and full structural characterization of thiocillin IV, a 26-membered thiopeptide. By inserting the tclO gene and genes responsible for micrococcin P2 production into a Bacillus strain, researchers achieved a production of 2.4 mg/L of culture. The purified thiocillin IV structure was identified as O-methylated micrococcin P2 at the 8-Thr position, showing promising biological activity against various Gram-positive pathogens.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hideaki Oikawa, Yusuke Mizunoue, Takemichi Nakamura, Eri Fukushi, Jiang Yulu, Taro Ozaki, Atsushi Minami
Summary: This study elucidates the structure and biosynthetic pathway of Albopeptins produced by Streptomyces albofaciens JC-82-120 using degradation, chemical synthesis, NMR data analysis, and bioinformatics analysis.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Yongwei Zhao, Y. T. Candace Ho, Julien Tailhades, Max Cryle
Summary: Researchers are intrigued by the complex biosynthesis of glycopeptide antibiotics, particularly the role of the X-domain in recruiting P450 enzymes. In vitro studies have provided insights into the tolerances and limitations of the GPA cyclisation cascade, paving the way for future reengineering of this important antibiotic class.
Article
Chemistry, Medicinal
Robert J. J. Stankey, Don Johnson, Brendan M. M. Duggan, David A. A. Mead, James J. J. La Clair
Summary: As one of the earliest marine natural products undergoing clinical trials, didemnin depsipeptides have played a significant role in inspiring the discovery of marine drugs. Originally developed for anticancer therapeutics, these compounds have recently been re-evaluated and advanced towards antiviral applications. While traditionally associated with colonial tunicates, their biosynthesis has now been found in the marine-derived bacteria Tistrella mobilis, although its low production and limited understanding hinder effective microbial or synthetic biological approaches. This study conducted a survey of Tistrella species and successfully developed conditions for the production of didemnin B at high titers.
Review
Chemistry, Multidisciplinary
Carter N. Stout, Hans Renata
Summary: Biocatalytic transformations are powerful tools for constructing complex natural products, enabling the incorporation of stereochemistry in synthetic campaigns. By leveraging enzymes, synthetic chemists can expand the chiral pool and simplify synthesis processes.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Sebastian L. Wenski, Sirinthra Thiengmag, Eric J. N. Helfrich
Summary: Complex peptide natural products have diverse functions and properties, and can be biosynthesized through ribosomally synthesized and post-translationally modified peptide (RiPP) biosynthetic pathways and non-ribosomal peptide synthetases (NRPSs). Understanding these pathways has led to universal principles for targeted identification of peptide biosynthetic blueprints and rational engineering of biosynthetic pathways. This review contrasts the key principles of both routes and compares different strategies for peptide modifications.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Esther J. Han, Seoung Rak Lee, Shotaro Hoshino, Mohammad R. Seyedsayamdost
Summary: Microorganisms have been a valuable source of therapeutically important natural products. This study utilized high-throughput elicitor screening to uncover cryptic metabolites with antiproliferative activity, leading to the discovery of novel bioactive compounds. These findings demonstrate the untapped potential of microbial strains in providing new molecules for cancer treatment.
ACS CHEMICAL BIOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Uli Kazmaier
Summary: Bottromycins, discovered in the mid-20th century, represent a unique class of natural products that have posed challenges in terms of structure elucidation and synthesis. Recent studies suggest that they belong to ribosomally synthesized and posttranslationally modified peptides, with a biosynthetic pathway that deviates from the norm.
ISRAEL JOURNAL OF CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
A. R. Ola Pasternak, Marcy J. Balunas, David L. Zechel
Summary: A hybrid gene cluster producing a glucosylated tubercidin derivative was identified in Streptomyces sp. AVP053U2 using a genome mining approach. A gene called avpGT was found within this cluster, which encodes a glucosyltransferase that has high specificity for UDP-glucose and transfers the glucose moiety to tubercidin. This study reveals the importance of understanding and producing glycosylated nucleoside compounds.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Milda Kaniusaite, Julien Tailhades, Tiia Kittila, Christopher D. Fage, Robert J. A. Goode, Ralf B. Schittenhelm, Max J. Cryle
Summary: The biosynthesis of glycopeptide antibiotics demonstrates the exceptional ability of nonribosomal peptide synthesis to generate diverse and complex structures. An important study on the NRPS assembly lines involved in synthesizing GPAs revealed that they function as dynamic peptide assembly lines, allowing for flexible control over amino acid modifications and peptide formation, which is beneficial for the redesign of important biosynthetic systems.
Article
Plant Sciences
Qiyao Shen, Guangzhi Dai, Vinothkannan Ravichandran, Yang Liu, Lin Zhong, Haiyan Sui, Xiangmei Ren, Nianzhi Jiao, Youming Zhang, Haibo Zhou, Xiaoying Bian
Summary: Siderophores are secreted by microorganisms to survive in iron-depleted conditions and have therapeutic potential. Eight amphiphilic siderophores, saccharochelins A-H, were identified from a rare marine-derived Saccharothrix species and showed cytotoxicity against human tumor cell lines. The fatty acid side chains of saccharochelins significantly affected cytotoxicity, indicating potential for producing more potent derivatives.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Chemistry, Organic
Jiafan Yang, Yongxiang Song, Man-Cheng Tang, Mingzhe Li, Junwei Deng, Nai-Kei Wong, Jianhua Ju
Summary: A genome-directed discovery strategy was used to identify 11 new tetrahydroisoquinolines (THIQs) from deep-sea derived Streptomyces, including aclidinomycins A and B as well as nine new compounds. The complex structures of these compounds, which contain unique polycyclic motifs, were elucidated through extensive spectroscopic analyses. Additionally, a proposed biosynthetic route and preliminary survey of their antimicrobial activities were reported.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Biotechnology & Applied Microbiology
Xin Pan, Lei Xu, Yaru Li, Sihua Wu, Yong Wu, Wenping Wei
Summary: This paper systematically reviews the strategies adopted in the past 20 years to improve the biosynthesis of beta-lactam antibiotics through adjusting enzymatic properties and manipulating the reaction system. These strategies include enzyme mining, protein engineering, solvent engineering, in situ product removal, and one-pot reaction cascade. These advances provide important guidelines for future industrial production of beta-lactam antibiotics using enzymatic synthesis.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Helen G. Smith, Matthew J. Beech, Jozef R. Lewandowski, Gregory L. Challis, Matthew Jenner
Summary: PKS and NRPS multienzymes produce valuable metabolites, with protein subunits requiring ordered self-assembly for correct organisation of catalytic domains. DDs at the N- and C-termini of each subunit interact in complementary pairs to facilitate substrate transfer and pathway fidelity. efforts to engineer biosynthetic pathways have focused on utilizing DDs.
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Kenan A. J. Bozhueyuek, Jonas Watzel, Nadya Abbood, Helge B. Bode
Summary: This study presents a strategy for functionally combining NRPS fragments from different sources to synthesize novel peptides. The synthetic NRPS (type S) introduced in this study allows for easier engineering, overcomes cloning limitations, and provides a simple and rapid approach to building peptide libraries through the combination of different NRPS subunits.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biotechnology & Applied Microbiology
Daniel Zabala, Lijiang Song, Yousef Dashti, Gregory L. Challis, Jose Salas, Carmen Mendez
MICROBIAL CELL FACTORIES
(2020)
Article
Multidisciplinary Sciences
Alice M. Banks, Lijiang Song, Gregory L. Challis, Andy M. Bailey, Gary D. Foster
Article
Microbiology
Paul G. Becher, Vasiliki Verschut, Maureen J. Bibb, Matthew J. Bush, Bela P. Molnar, Elisabeth Barane, Mahmoud M. Al-Bassam, Govind Chandra, Lijiang Songs, Gregory L. Challis, Mark J. Buttner, Klas Flardh
NATURE MICROBIOLOGY
(2020)
Article
Chemistry, Multidisciplinary
Yousef Dashti, Ioanna T. Nakou, Alex J. Mullins, Gordon Webster, Xinyun Jian, Eshwar Mahenthiralingam, Gregory L. Challis
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2020)
Article
Genetics & Heredity
Cerith Jones, Gordon Webster, Alex J. Mullins, Matthew Jenner, Matthew J. Bull, Yousef Dashti, Theodore Spilker, Julian Parkhill, Thomas R. Connor, John J. LiPuma, Gregory L. Challis, Eshwar Mahenthiralingam
Summary: Burkholderia gladioli is a diverse bacterium with significant ecological impacts on humans, animals, and plants, spanning diseases and beneficial interactions. Through exploring its genomic diversity and metabolic potential, it has shed light on its roles as a plant pathogen, food poisoning agent, and lung pathogen for CF patients. This research has identified potential therapeutic strategies to minimize poisoning risks associated with this bacterium.
MICROBIAL GENOMICS
(2021)
Review
Biotechnology & Applied Microbiology
Helen G. Smith, Matthew J. Beech, Jozef R. Lewandowski, Gregory L. Challis, Matthew Jenner
Summary: PKS and NRPS multienzymes produce valuable metabolites, with protein subunits requiring ordered self-assembly for correct organisation of catalytic domains. DDs at the N- and C-termini of each subunit interact in complementary pairs to facilitate substrate transfer and pathway fidelity. efforts to engineer biosynthetic pathways have focused on utilizing DDs.
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Shanshan Zhou, Hussain Bhukya, Nicolas Malet, Peter J. Harrison, Dean Rea, Matthew J. Belousoff, Hariprasad Venugopal, Paulina K. Sydor, Kathryn M. Styles, Lijiang Song, Max J. Cryle, Lona M. Alkhalaf, Vilmos Fulop, Gregory L. Challis, Christophe Corre
Summary: Actinobacteria produce antibiotics and hormones with important applications in medicine and agriculture. Hormones control the production of metabolites by binding TFTRs, but the molecular basis for this process remains unclear. This study elucidates the structural basis for hormone recognition and the mechanism for DNA release upon hormone binding, providing insights into the role of individual amino acid residues and hormone functional groups in ligand recognition and DNA release.
Article
Biochemistry & Molecular Biology
Rakesh Saroay, Gheorghe-Doru Roiban, Lona M. Alkhalaf, Gregory L. Challis
Summary: The variant R59C of TxtE has a broader substrate scope, allowing it to nitrate a range of tryptamine analogues. This presents a new direction for developing TxtE into a useful aromatic nitration biocatalyst.
Article
Multidisciplinary Sciences
Thierry Izore, Y. T. Candace Ho, Joe A. Kaczmarski, Athina Gavriilidou, Ka Ho Chow, David L. Steer, Robert J. A. Goode, Ralf B. Schittenhelm, Julien Tailhades, Manuela Tosin, Gregory L. Challis, Elizabeth H. Krenske, Nadine Ziemert, Colin J. Jackson, Max J. Cryle
Summary: Non-ribosomal peptide synthetases (NRPSs) are essential for assembling complex natural products, with condensation domains playing a central role in chain assembly. Structural snapshots of a condensation domain bound to an aminoacyl-PCP substrate reveal a mechanism for controlling substrate access and tuning selectivity, without requiring a distinct pocket for side chain selection during peptide assembly.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Juan Pablo Gomez-Escribano, Neil A. Holmes, Susan Schlimpert, Maureen J. Bibb, Govind Chandra, Barrie Wilkinson, Mark J. Buttner, Mervyn J. Bibb
Summary: Streptomyces venezuelae has been widely used as a model strain for studying molecular mechanisms controlling morphological development in streptomycetes. Its rapid growth and ability to sporulate in a near-synchronized manner in liquid culture make it suitable for modern molecular techniques. A high-quality genome sequence of the strain was described, revealing differences in spore pigmentation and the successful use of CRISPR-Cas9 to cure the plasmid without noticeable phenotypic consequences.
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
(2021)
Article
Chemistry, Organic
Jieyan Lim, Venkaiah Chintalapudi, Haraldur G. Gudmundsson, Minh Tran, Alice Bernasconi, Araceli Blanco, Lijiang Song, Gregory L. Challis, Edward A. Anderson
Summary: Stambomycins are bioactive macrolides isolated from Streptomyces ambofaciens, with their stereochemistry predicted by sequence analysis of the polyketide synthase. The synthesis of the C1-C27 fragment of stambomycin D matched well with the natural product's spectroscopic data, confirming the effectiveness of predictive sequence analysis in stereochemical assignment of complex polyketide natural products.
Article
Microbiology
Alex J. Mullins, Jinlian Zhao, Gordon Webster, Hak Joong Kim, Yoana D. Petrova, Christina E. Ramming, Matthew Jenner, James A. H. Murray, Thomas R. Connor, Christian Hertweck, Gregory L. Challis, Eshwar Mahenthiralingam
Summary: The study revealed the widespread distribution of natural products with alkyne and polyyne moieties in bacteria, with their biosynthetic gene clusters showing evolutionary connections. Through genomic and phylogenetic analyses, the diversity and biosynthetic logic of polyyne were explored, providing insights into discovering new natural products and enhancing the understanding of polyyne synthesis.
Article
Chemistry, Organic
Yongchen Wang, Venkaiah Chintalapudi, Haraldur G. Gudmundsson, Gregory L. Challis, Edward A. Anderson
Summary: The stereochemical assignment of macrolide antibiotics stambomycins A-D was based on sequence analysis of the associated polyketide synthase, except for two stereocentres at C28 and C50. The synthesis of two C50 diastereomers of the C33-C51 region of the stambomycins confirms the PKS-based configurational assignment and establishes a strategy for accessing the extended stambomycin framework.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Genetics & Heredity
Juan Pablo Gomez-Escribano, Lis Algora Gallardo, Kenan A. J. Bozhuyuk, Steven G. Kendrew, Benjamin D. Huckle, Nicola A. Crowhurst, Mervyn J. Bibb, Andrew J. Collis, Jason Micklefield, Paul R. Herron, Barrie Wilkinson
Summary: Streptomyces clavuligerus is an industrially important actinomycete with genetic manipulation limitations. Through Cas9-mediated genome editing, successful curing of pSCL4 revealed its crucial role in the structural stability of the linear chromosome.
MICROBIAL GENOMICS
(2021)
Article
Biochemistry & Molecular Biology
Christian Hobson, Matthew Jenner, Xinyun Jian, Daniel Griffiths, Douglas M. Roberts, Matias Rey-Carrizo, Gregory L. Challis
Summary: This study reports the discovery of a new variant of a dehydratase domain that eliminates two molecules of water in sequential steps during polyketide chain assembly, leading to the introduction of a conjugated E,Z-diene. These findings expand the catalytic versatility of modular PKSs and highlight the role of a conserved histidine residue in the reaction.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Alexander M. Prophet, Kritanjan Polley, Gary J. Van Berkel, David T. Limmer, Kevin R. Wilson
Summary: The oxidation kinetics of iodide by ozone at the air-water interface is studied in single microdroplets. Molecular simulations and kinetic modeling are used to understand the underlying multiphase mechanism.
Article
Chemistry, Multidisciplinary
Rong Zhang, Jiajing Lan, Fei Wang, Shumei Chen, Jian Zhang
Summary: By utilizing 1,1'-ferrocene dicarboxylic acid as a chelating and surface protection ligand, we have synthesized multi-nuclear indium oxide clusters with varying nuclear sizes, including heptanuclear and thirteen-nuclear clusters. These clusters possess labile coordination sites, allowing for structural modification and self-assembly, resulting in the formation of various cluster structures.
Article
Chemistry, Multidisciplinary
Hui Wang, Hui Liu, Mingsen Wang, Jiaheng Hou, Yongjun Li, Yuancheng Wang, Yingjie Zhao
Summary: Two supramolecular complexes were prepared using CBs and M1, and their single-crystal structures were analyzed by SCXRD. The unexpected 1:2 self-assembly structure between M1 and CB[8] was discovered for the first time. These complexes exhibit unique photophysical properties and provide valuable information about the structure and photophysical properties of supramolecular complexes.
Article
Chemistry, Multidisciplinary
Chang-Hee Lee, Sookil Park, Sanggil Kim, Ji Young Hyun, Hyun Soo Lee, Injae Shin
Summary: The epidermal growth factor receptor (EGFR) is a cell-surface glycoprotein involved in cell proliferation and tumor development. This study used a fluorescently labeled EGFR to investigate its time-dependent endocytosis in live cells and found that appended glycans affect EGFR internalization. Additionally, the study detected sialic acid residues attached to EGFR on the live cell surface using FRET-based imaging. This research provides valuable insights into the cellular functions of EGFR.
Article
Chemistry, Multidisciplinary
Subhankar Sahu, Lokesh Kumar, Sumita Das, Dipti Gupta, Ruchi Anand
Summary: This study proposes a strategy that combines organic electronics with biosensor scaffolds to create a compact device for monitoring environmental aromatic pollution. By coupling biosensing protein MopR with an organic electrochemical transistor (OECT), a sensor module capable of efficient detection of phenol was designed. Exclusive phenol detection with minimal loss of sensitivity could be achieved in complex pollutant mixtures and real environmental samples.
Review
Chemistry, Multidisciplinary
Changseok Lee, Hyung-Joon Kang, Sungwoo Hong
Summary: The formation of C-N bonds through hydroamination reactions catalyzed by nickel hydrides has been a topic of recent interest. This approach offers a way to efficiently transform a variety of alkene and alkyne substrates into compounds enriched with C-N bonds. The review provides a concise overview of the underlying reaction mechanisms and aims to stimulate further progress in NiH-catalytic techniques and catalyst design.
Article
Chemistry, Multidisciplinary
Yueci Wu, Lu-Lu Sun, Hai-Hao Han, Xiao-Peng He, Weiguo Cao, Tony D. James
Summary: Drug-induced liver injury (DILI) is a common cause of acute liver failure in the USA and Europe, but most cases can be recovered or prevented by discontinuing the offending drug. Recent research has found that peroxynitrite (ONOO-) can be used as a potential indicator for early diagnosis of DILI, and there is an urgent need to establish a method to detect and track peroxynitrite in DILI cases. In this study, a FRET-based nano fluorescent probe CD-N-I was developed, which showed high selectivity and sensitivity in detecting peroxynitrite. The probe successfully detected exogenous peroxynitrite in live cells and endogenous peroxynitrite in APAP-induced liver injury of HepG2 cells.
Article
Chemistry, Multidisciplinary
Dmitry L. Lipilin, Mikhail O. Zubkov, Mikhail D. Kosobokov, Alexander D. Dilman
Summary: This article describes a direct photocatalytic method for the thiolation of unprotected acids, which was previously challenging. By using a thionocarbonate reagent with an N-O bond, the efficient conversion of carboxylic acids to thiols is achieved.
Article
Chemistry, Multidisciplinary
Jason Malenfant, Lucille Kuster, Yohann Gagne, Kouassi Signo, Maxime Denis, Sylvain Canesi, Mathieu Frenette
Summary: Raman microscopy can reveal compound-specific vibrational fingerprints without sample preparation. The combination of efficient theoretical calculations and a user-friendly software can accurately predict peak positions and provide match scores to assist with structure determination.
Article
Chemistry, Multidisciplinary
Jayoh A. Hernandez, Paul S. Micus, Sean Alec Lois Sunga, Luca Mazzei, Stefano Ciurli, Gabriele Meloni
Summary: Essential trace metals play crucial roles in the survival and virulence of bacterial pathogens. Helicobacter pylori requires nickel for colonization and persistence in the stomach, and NixA is an essential nickel transporter in this process. This study characterizes the selectivity and electrogenic nature of NixA-mediated nickel transport.
Article
Chemistry, Multidisciplinary
Tarali Devi, Kuheli Dutta, Jennifer Deutscher, Stefan Mebs, Uwe Kuhlmann, Michael Haumann, Beatrice Cula, Holger Dau, Peter Hildebrandt, Kallol Ray
Summary: This study emphasizes the importance of subtle electronic changes and secondary interactions in the stability of biologically relevant metal-dioxygen intermediates. It also shows that the role of the chloride ligand in stabilizing the Fe-III-(OOBu)-Bu-t moiety can extend to other anions, including the thiolate ligand.
Article
Chemistry, Multidisciplinary
Jacqueline R. Santhouse, Jeremy M. G. Leung, Lillian T. Chong, W. Seth Horne
Summary: By studying the folding kinetics and mechanism of the BdpA sequence, researchers found that altering the backbone connectivity can affect protein folding. This suggests that protein mimetic chains have a significant degree of plasticity in transitioning between unfolded and folded states.
Article
Chemistry, Multidisciplinary
Divanshu Gupta, Ralf Einholz, Holger F. Bettinger
Summary: This study presents the first direct spectroscopic evidence of a cyclic seven-membered iminoborane. Compared to linear amino-iminoboranes, this cyclic iminoborane exhibits weakened bond strength and lower Lewis acidity value. The study suggests that the reduced ring strain of cyclic iminoborane prevents nitrogen fixation but allows facile (2 + 2) cycloaddition reaction with C2H4.
Article
Chemistry, Multidisciplinary
Renny Mathew, Aniruddha Mazumder, Praveen Kumar, Julie Matula, Sharmarke Mohamed, Petr Brazda, Mahesh Hariharan, Brijith Thomas
Summary: This study reveals the packing arrangement of partially disordered nitro-perylenediimide (NO2-PDI) using a synergistic approach that combines 3D ED, ssNMR, and DFT techniques. By overcoming these challenges, this methodology opens up new avenues for material characterization, driving exciting advancements in the field.