Article
Chemistry, Multidisciplinary
Nikolai A. Loehr, Frederic Eisen, Wiebke Thiele, Lukas Platz, Jonas Motter, Wolfgang Huettel, Markus Gressler, Michael Mueller, Dirk Hoffmeister
Summary: This study describes an unprecedented class of non-reducing polyketide synthases (NR-PKS) that can synthesize octaketide pigments. The researchers identified CoPKS1 and CoPKS4 of the mushroom genus Cortinarius as new atrochrysone carboxylic acid synthases. These findings illustrate how the biosynthesis of bioactive metabolites evolved independently in different groups of organisms.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Biotechnology & Applied Microbiology
Chang Liu, Sijin Li
Summary: This review summarizes the progress made in the past 10 years in type III PKS-catalyzed natural product biosynthesis in microorganisms, with a focus on complete biosynthesis strategies and achievements.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shreya Kishore, Chaitan Khosla
Summary: By mining genomic data from the NCBI database, this study presents an updated catalogue of 8799 non-redundant assembly line polyketide synthase clusters across 4083 species, showing a threefold increase in the past 4 years. Furthermore, 95% of the clusters are 'orphan clusters' with no known chemical or biological characterization. These findings suggest that the diversity of assembly line PKSs remains largely unexplored and highlight the potential of genomics-driven approaches for natural product discovery.
Article
Biochemistry & Molecular Biology
Fumitaka Kudo, Kosuke Kishikawa, Kazuma Tsuboi, Takafusa Kido, Takeo Usui, Junko Hashimoto, Kazuo Shin-ya, Akimasa Miyanaga, Tadashi Eguchi
Summary: In this study, the biosynthetic gene cluster for virustomycin A, an antibiotic produced by Streptomyces graminofaciens A-8890, was identified. The study also demonstrated the exchangeability of the acyltransferase domain between the PKSs involved in FD-891 biosynthesis and the Vsm PKSs. By exchanging the malonyltransferase domain in the loading module of the PKSs, a two-carbon-elongated analog 26-ethyl-FD-891 was successfully produced with potent cytotoxic activity.
Article
Chemistry, Multidisciplinary
Ashley J. Winter, Matthew T. Rowe, Angus N. M. Weir, Nahida Akter, Sbusisiwe Z. Mbatha, Paul D. Walker, Christopher Williams, Zhongshu Song, Paul R. Race, Christine L. Willis, Matthew P. Crump
Summary: In this study, the remaining steps of 9HN biosynthesis were investigated using NMR spectroscopy, mass spectrometry, chemical probes, and in vitro assays. The results reveal a complex interplay between multiple acyl carrier proteins and a novel KS-AT didomain.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Aleksandra Nivina, Sur Herrera Paredes, Hunter B. Fraser, Chaitan Khosla
Summary: A genetic element named GRINS has been found in assembly-line PKS genes, potentially accelerating the diversification of related biosynthetic clusters, especially prevalent in the actinobacterial genus Streptomyces.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Organic
Ruijie Huang, Xiaolu Meng, Kaixiang Tao, Mingming Cao, Lishuang Nie, Yao Dong, Yunbin Lyu, Shaochen Wang, Zhiyang Feng
Summary: A novel benz[h]isoquinoline-desfer-rioxamine B conjugated compound amodesmycins was isolated from Streptomyces albus J1074 harboring the amd gene cluster. The genetic evidence showed that the amd gene cluster and S. albus J1074 were responsible for the synthesis of different parts of amodesmycins, and P450 enzymes played critical roles in their conjunction.
Article
Biotechnology & Applied Microbiology
Enjuro Harunari, Maho Bando, Yasuhiro Igarashi
Summary: A new pluramycin-class polyketide compound named rausuquinone with antimicrobial activity was isolated from the culture extract of deep-sea water-derived Rhodococcus sp. RD015140, along with a known congener hydramycin. The structure of rausuquinone was determined through extensive NMR analysis, showing a gamma-pyrone-fused anthraquinone core. This discovery marks the first identification of aromatic polyketides from the genus Rhodococcus.
JOURNAL OF ANTIBIOTICS
(2022)
Article
Plant Sciences
Gabriel Castro-Falcon, Kaitlin E. Creamer, Alexander B. Chase, Min Cheol Kim, Douglas Sweeney, Evgenia Glukhov, William Fenical, Paul R. Jensen
Summary: A new manumycin-type natural product named pacificamide (1) and its potential biosynthetic gene cluster (pac) were discovered from the marine actinobacterium Salinispora pacifica CNT-855. This study also reported the synthesis of the known metabolite triacsin D from the genus Salinispora. These findings enrich the model of natural product research in the genus Salinispora.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Plant Sciences
Wei Zhou, Priyapan Posri, Xiao-Jing Liu, Zhiran Ju, Wen-Jian Lan, Taifo Mahmud
Summary: The soil bacterium Streptomyces pactum ATCC 27456 produces polyketide natural products, including NFAT-133, an inhibitor of NFAT that suppresses IL-2 expression. Inactivation of biosynthetic genes in this strain revealed its ability to produce analogues of NFAT-133. Several new derivatives of NFAT-133 were isolated, along with a known compound, panowamycin A, which showed no antibacterial activity but weakly reduced nitric oxide production in cells.
JOURNAL OF NATURAL PRODUCTS
(2021)
Review
Chemistry, Multidisciplinary
Tegan P. Stockdale, Nelson Y. S. Lam, Matthew J. Anketell, Ian Paterson
Summary: The diverse and complex structures of polyketide natural products have inspired synthetic chemists for decades. This review summarizes a thirty-year journey into the total synthesis of 18 polyketide natural products, highlighting the unique challenges and discoveries encountered along the way, with a focus on the crucial role of highly selective aldol reactions in configuring the densely oxygenated stereoclusters.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2021)
Editorial Material
Biochemistry & Molecular Biology
Zhiyang Feng
Summary: In this study, Huber et al. identify five O-methyltransferases, with three of them sequentially methylating the Gram-negative bacterium-derived aromatic polyketide anthraquinone AQ-256. They analyze the co-crystal structures of AQ-256 and its methylated derivatives, providing insights into the specificities of these O-methyltransferases.
Article
Multidisciplinary Sciences
Hongjiao Zhang, Zixin Li, Shuang Zhou, Shu-Ming Li, Huomiao Ran, Zili Song, Tao Yu, Wen-Bing Yin
Summary: FnsA is a novel NRPS-PKS hybrid that is involved in the formation of naringenin. It activates both p-coumaric acid and p-hydroxybenzoic acid through its adenylation domain and uses malonyl-CoA molecules for elongation. Refactoring the biosynthetic pathway with fnsA in yeast provides an alternative approach for the production of flavonoids such as isorhamnetin and acacetin.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Yunjun Pan, Guobang Li, Ruxin Liu, Jiawei Guo, Yunjie Liu, Mingyu Liu, Xingwang Zhang, Luping Chi, Kangwei Xu, Ruibo Wu, Yuzhong Zhang, Yuezhong Li, Xiang Gao, Shengying Li
Summary: Cytochrome P450 enzymes play crucial roles in the biosynthesis of macrolide antibiotics. However, the 20 proteinogenic amino acids may not always meet the requirements of site-directed/random mutagenesis and rational protein design. In this study, the authors employed semi-rational non-canonical amino acid mutagenesis to improve the enzyme's activity and gain mechanistic insights.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Yiwei Li, Megan Reed, H. Tonie Wright, T. Ashton Cropp, Gavin J. Williams
Summary: Clarithromycin is an improved semisynthetic analogue of erythromycin, with enhanced acid stability. By evolving the effector specificity of MphR protein, selective recognition of clarithromycin was achieved, providing insights for the evolution of new metabolic functions using this biosensor.
ACS SYNTHETIC BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Sydney P. Thomas, Erce Denizer, Simone Zuffa, Brookie M. Best, Lars Bode, Christina D. Chambers, Pieter C. Dorrestein, George Y. Liu, Jeremiah D. Momper, Victor Nizet, Shirley M. Tsunoda, Adriana H. Tremoulet
Summary: Antibiotics are crucial for perinatal care, but they can harm the host gut microbiota. Current studies mainly focus on the effects of antibiotics on infants directly or through maternal use, with limited knowledge about the risks of antibiotics in human milk to infants.
Article
Microbiology
Ericka Anderson, Bipin Nair, Victor Nizet, Geetha Kumar
Summary: The complexity of antimicrobial resistance (AMR) crisis and its global impact on healthcare requires understanding of the underlying forces and implementation of innovative solutions. Future therapeutic interventions should focus on host-pathogen interactions to enhance the innate immune system and reduce pathogen virulence. Interrupting pathogen survival strategies and using clonotyping assays to identify 'super clones' can guide targeted antibiotic regimens. Innovative alternatives to traditional antibiotics, such as bacteriophage therapy and repurposing drugs, are being successfully used to combat AMR. Policy changes, including shorter durations of antibiotic treatment and increased surveillance measures, can enhance patient safety and global prevention and control programs.
JOURNAL OF MEDICAL MICROBIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yern-Hyerk Shin, Ji Hyeon Im, Ilnam Kang, Eunji Kim, Sung Chul Jang, Eunji Cho, Daniel Shin, Sunghoon Hwang, Young Eun Du, Thanh-Hau Huynh, Keebeom Ko, Yoon-Joo Ko, Sang-Jip Nam, Takayoshi Awakawa, Jeeyeon Lee, Suckchang Hong, Ikuro Abe, Bradley S. Moore, William Fenical, Yeo Joon Yoon, Jang-Cheon Cho, Sang Kook Lee, Ki-Bong Oh, Dong-Chan Oh
Summary: By combining genomic signature-based PCR screening and spectroscopic signature-based early identification, a targeted discovery method for natural macrolactams was developed. This method allowed efficient selection of potential macrolactam-producing strains and enabled structural confirmation without purification steps.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Biochemistry & Molecular Biology
Takayoshi Awakawa, Takahiro Mori, Richiro Ushimaru, Ikuro Abe
Summary: Non-heme iron- and alpha-ketoglutarate-dependent oxygenases (alpha KG OXs) are important enzymes in diversifying the structure of fungal meroterpenoids. They activate specific C-H bonds to generate radical species, followed by oxygen rebound to produce hydroxylated products. Remarkable chemistry-induced structural changes in molecular scaffolds depend on the substrate/intermediates' stereoelectronic characters and the conformational changes/movements of the enzyme's active site.
NATURAL PRODUCT REPORTS
(2023)
Article
Immunology
E. Mauricio Barajas-Mora, Lindsay Lee, Hanbin Lu, J. Andres Valderrama, Elisabet Bjanes, Victor Nizet, Ann J. J. Feeney, Ming Hu, Cornelis Murre
Summary: Researchers have identified a specific enhancer, E34, within the Igk locus, which is crucial for chromatin remodeling and repositioning, and promotes the rearrangement of Igkv7-33 V-kappa-J(kappa) genes necessary for the production of anti-phosphorylcholine-specific antibodies. Mice lacking E34 are more susceptible to Streptococcus pneumoniae infections.
Article
Biology
Takayoshi Awakawa, Wei Liu, Tongxuan Bai, Tomo Taniguchi, Ikuro Abe
Summary: In this study, the biosynthetic pathway of the fungal meroterpenoid austalide F, which contains an orthoester functionality, was elucidated through heterologous gene expression in Aspergillus oryzae and in vitro assays. The alpha-ketoglutarate-dependent oxygenase AstB was found to produce the hemiacetal intermediate, and the methyltransferase AstL was responsible for transferring a methyl group to construct the orthoester functionality. These findings highlight the extraordinary biosynthetic machinery of orthoester-containing fungal meroterpenoids and provide valuable insights for the engineered biosynthesis of unnatural bioactive meroterpenoids.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Engineering, Biomedical
Elisabet Bjanes, Jiarong Zhou, Tariq Qayum, Nishta Krishnan, Raymond H. Zurich, Nitasha D. Menon, Alexandria Hoffman, Ronnie H. Fang, Liangfang Zhang, Victor Nizet
Summary: This study reports a vaccine platform that combines gold nanoparticles coated with immunogenic Acinetobacter baumannii outer membrane vesicles (Ab-OMVs). It induces high levels of IgG antibodies in rabbits, enhances neutrophil killing of A. baumannii, and provides passive protection against sepsis in mice. Active immunization with the Ab-NP vaccine in mice protects against sepsis and pneumonia, activates B cells and dendritic cells, improves neutrophil responses, and mitigates cytokine storm.
ADVANCED NANOBIOMED RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Jennifer H. Wisecaver, Robert P. Auber, Amanda L. Pendleton, Nathan F. Watervoort, Timothy R. Fallon, Olivia L. Riedling, Schonna R. Manning, Bradley S. Moore, William W. Driscoll
Summary: Harmful algal blooms of the toxic haptophyte Prymnesium parvum are a recurrent problem in many inland and estuarine waters around the world. Genomic analysis of 15 diverse strains of P. parvum revealed considerable DNA content variation and identified functional categories associated with metabolic and genome size variation. The results indicate the presence of multiple cryptic species within P. parvum and highlight the need for similar resources for other harmful algal-bloom-forming morphospecies.
Article
Infectious Diseases
Lucy Catteau, Yvan Diaz Iglesias, Hannah Tsunemoto, Joseph Pogliano, Francoise Van Bambeke, Victor Nizet, George Sakoulas
Summary: Methicillin-resistant Staphylococcus epidermidis (MRSE) endocarditis, which does not respond to conventional therapy, can be effectively treated with the combination of nafcillin and daptomycin. In vitro studies have shown that nafcillin enhances the killing of MRSE by daptomycin, both in planktonic cells and biofilms. Nafcillin also sensitizes MRSE to killing by human neutrophils and cathelicidin antimicrobial peptide LL-37. Clinical studies are needed to determine the optimal timing for the use of these regimens to improve clinical outcomes.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Multidisciplinary Sciences
Tirthankar Mohanty, Christofer A. Q. Karlsson, Yashuan Chao, Erik Malmstrom, Eleni Bratanis, Andrietta Grentzmann, Martina Morch, Victor Nizet, Lars Malmstrom, Adam Linder, Oonagh Shannon, Johan Malmstrom
Summary: This study used pharmacoproteomics to evaluate the time-dependent treatment effects of meropenem and methylprednisolone on a murine Escherichia coli sepsis model. Three distinct proteome response patterns were identified, which depended on the underlying proteotype for each organ. The findings provide insights for guiding treatment timing, dosage, and potential combination therapies.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
April L. Lukowski, Felix M. Hubert, Thuan-Ethan Ngo, Nicole E. Avalon, William H. Gerwick, Bradley S. Moore
Summary: We report the discovery and characterization of an alkynyl halogenase, JamD, which is capable of terminal alkyne halogenation and has broad substrate tolerance. This finding has significant implications for the development of chemoselective biocatalysts, such as the synthesis of haloalkynes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Microbiology
Amanda T. Alker, Morgan V. Farrell, Alpher E. Aspiras, Tiffany L. Dunbar, Andriy Fedoriouk, Jeffrey E. Jones, Sama R. Mikhail, Gabriella Y. Salcedo, Bradley S. Moore, Nicholas J. Shikuma
Summary: In this study, a modular plasmid toolkit was adapted for use in 12 marine bacteria, and a marine Pseudoalteromonas bacterium was successfully engineered to study its association with its host animal. This work demonstrates the potential of modular genetic tools to be applied to diverse marine bacteria for basic science research and biotechnology innovations.
Article
Chemistry, Physical
Jennifer L. L. Cordoza, Percival Yang-Ting Chen, Linnea R. R. Blaustein, Stella T. T. Lima, Marli F. F. Fiore, Jonathan R. R. Chekan, Bradley S. S. Moore, Shaun M. K. McKinnie
Summary: Researchers have discovered and characterized the biosynthetic pathway of guanitoxin, a neurotoxin containing a cyclic arginine derivative. By comparing the structures and activities, they have identified the amino acid residues that contribute to the catalytic mechanism. This study provides a better understanding of how nature produces cyclic arginine noncanonical amino acids and offers tools for their biocatalytic production and biological applications.
Article
Biology
Sarah R. Rudd, Leticia Silva Miranda, Hannah R. Curtis, Yves Bigot, Mercedes Diaz-Mendoza, Robert Hice, Victor Nizet, Hyun-Woo Park, Gregor Blaha, Brian A. Federici, Dennis K. Bideshi
Summary: This paper introduces three important commercial bacterial insecticides derived from different subspecies of Bacillus thuringiensis (Bt), including their sources and uses. It also explores the unique features of Bt subspecies israelensis, such as the structure of the parasporal body (PB) and the multilaminar fibrous matrix (MFM), as well as the functions and structural similarities of two proteins, Bt152 and Bt075. Additionally, a novel molecular process for targeting Cry and Cyt proteins has been identified.
Article
Ecology
Amanda T. Alker, Morgan V. Farrell, Alyssa M. Demko, Trevor N. Purdy, Sanjoy Adak, Bradley S. Moore, Jennifer M. Sneed, Valerie J. Paul, Nicholas J. Shikuma
Summary: The quality of bacteria associated with corals and coral reefs is crucial for coral fitness, as bacteria can stimulate the transition from larval to juvenile life cycle in corals. This study investigates the role of Tetrabromopyrrole (TBP), a small molecule produced by bacteria, in coral metamorphosis. The results show that the gene bmp2 is critical for TBP biosynthesis in the bacteria and its mutation affects the ability of the bacteria to stimulate coral metamorphosis. This study provides new genetic techniques to explore coral-bacteria interactions and has implications for coral restoration.
ISME COMMUNICATIONS
(2023)
