Article
Chemistry, Multidisciplinary
Therese Horch, Evelyn M. Molloy, Florian Bredy, Veit G. Haensch, Kirstin Scherlach, Kyle L. Dunbar, Jonathan Franke, Christian Hertweck
Summary: This study reports a previously overlooked biosynthetic pathway for benzoxazoles in anaerobic bacteria, expanding their chemical space and distribution range. The research reveals differences in biosynthesis between anaerobic bacteria and actinomycetes, and demonstrates the synthetic utility of the discovered pathway.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Microbiology
Meirong Ren, Shuhua Jiang, Yanyan Wang, Xinhua Pan, Feng Pan, Xinli Wei
Summary: Lichen natural products are a valuable resource for drug discovery, yet their utilization has been limited due to slow growth, low biomass availability, and technical challenges in cultivation. To overcome these challenges, the OSMAC strategy has been developed to activate silent or cryptic biosynthetic gene clusters and exploit lichen compounds for industrial applications. Additionally, advancements in molecular network techniques and genetic tools provide opportunities for mining, modifying, and producing lichen metabolites.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Shanchong Chen, Chi Zhang, Lihan Zhang
Summary: This study provides a global atlas of bacterial aromatic polyketides based on large-scale analysis of type II polyketide synthases. The chain length factor protein is identified as a marker that can predict the chemical class and molecular uniqueness of the biosynthetic product. The results serve as a compass for exploiting the entire type II polyketide synthase-derived aromatic polyketides in bacteria.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biotechnology & Applied Microbiology
Tao Zhang, Guowei Cai, Xiaoting Rong, Jingwen Xu, Bingya Jiang, Hao Wang, Xinxin Li, Lu Wang, Ran Zhang, Wenni He, Liyan Yu
Summary: Genomic analysis revealed the presence of numerous biosynthetic gene clusters in ascomycetes, with the study identifying the epi cluster responsible for epicoccamide A biosynthesis in Epicoccum sp. CPCC 400996 through genetic deletion and bioinformatic analysis. The study proposed a metabolic pathway for epicoccamide A biosynthesis and highlighted the potential for derivatization or generation of new chemical entities based on these findings.
MICROBIAL CELL FACTORIES
(2022)
Article
Engineering, Chemical
Qiuyue Nie, Shuqi Guo, Xue Gao
Summary: We report the discovery of the biosynthetic gene cluster for penicillenol A(1) and E in Penicillium citrinum and propose the assembly line of the polyketide synthase module in PncA and the formation mechanism of penicillenol A(1).
Article
Chemistry, Multidisciplinary
Stella T. Lima, Brigitte G. Ampolini, Ethan B. Underwood, Tyler N. Graf, Cody E. Earp, Imani C. Khedi, Michael A. Pasquale, Jonathan R. Chekan
Summary: Cyclopeptide alkaloids, a class of abundant plant cyclic peptides, have diverse bioactivities and over 200 analogs described. The biosynthetic basis of these natural products has remained unclear until now. Through transcriptome mining, researchers linked cyclopeptide alkaloids from Ceanothus americanus to dedicated RiPP precursor peptides and identified new gene clusters containing split BURP peptide cyclases. The discovery of arabipeptins from Coffea arabica and validation of BURP enzyme activity in the biosynthesis of arabipeptin A further expand our understanding of the biosynthetic pathways responsible for cyclic plant peptides.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Dongqi Yi, Vinayak Agarwal
Summary: Natural products containing the alpha-pyrone moiety are produced by polyketide synthases (PKSs) in bacteria, fungi, and plants. This study demonstrates that truncating a tetraketide natural product producing PKS assembly line allows for a thioesterase-independent off-loading of an alpha-pyrone polyketide natural product. By engineering the truncated PKS in vitro, it is shown that a ketosynthase (KS) domain with relaxed substrate selectivity can expand the chemical space of alpha-pyrone polyketide natural products.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Organic
Friederike Biermann, Sebastian L. Wenski, Eric J. N. Helfrich
Summary: Natural products are a valuable source of new drug leads due to their structural diversity and diverse biological activities. Genome mining is a computational approach that analyzes sequenced genomes to identify potential natural product biosynthetic gene clusters. Both hard-coded rules and machine learning algorithms have been developed as tools for gene cluster identification. This perspective article discusses the state-of-the-art genome mining tools, their confidence in predictions, and their potential to identify non-canonical gene clusters. Additionally, two indirect strategies for gene cluster identification are introduced. The combination of all existing genome mining approaches will contribute to a comprehensive understanding of the biosynthetic repertoire encoded in microbial genomes.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Katherine Williams, Claudio Greco, Andrew M. Bailey, Christine L. Willis
Summary: Azaphilones are a family of fungal natural products with interesting and useful bioactivities. Research has identified their biosynthetic pathways and proposed a consensus scheme. Consensus understanding of core enzymatic steps can aid in genome mining experiments.
Review
Biochemistry & Molecular Biology
Taro Shiraishi, Tomohisa Kuzuyama
Summary: Phosphonates are organic phosphorus compounds with a characteristic C-P bond, which serve as lead compounds for drug development. Fosfomycin, a widely-used antibacterial drug, has a complex biosynthetic pathway with recent breakthroughs. Genome mining and chemoenzymatic synthesis have expanded the repertoire of phosphonates and their biosynthetic machinery in recent years.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Mugilarasi Purushothaman, Snigdha Sarkar, Maho Morita, Muriel Gugger, Eric W. Schmidt, Brandon I. Morinaka
Summary: Genome mining was used to identify a novel cyanobactin metabolite tolypamide from the freshwater cyanobacterium Tolypothrix sp., which features an unprecedented post-translational prenylation modification on a threonine residue. The enzyme TolF shows strict selectivity for prenylation of serine or threonine, providing potential as a robust tool for synthetic biology.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
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
Multidisciplinary Sciences
Matthew T. Robey, Lindsay K. Caesar, Milton T. Drott, Nancy P. Keller, Neil L. Kelleher
Summary: This study provides detailed annotation and analysis of fungal biosynthetic and chemical space, enabling genome mining and discovery of fungal natural products. The taxonomic landscape of fungal gene cluster families is largely species specific, revealing dramatic differences between fungal and bacterial biosynthetic logic and chemical space.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biotechnology & Applied Microbiology
Caiyun Li, Khorshed Alam, Yiming Zhao, Jinfang Hao, Qing Yang, Youming Zhang, Ruijuan Li, Aiying Li
Summary: Antimicrobial resistance is a serious global issue, and the discovery of new natural products to combat multidrug-resistant pathogens is in high demand. Lanthipeptides, with their diverse chemical structures and mechanisms of action, are a valuable source of drug candidates that can be discovered through genome mining and biosynthetic engineering. This review covers recent advances in the discovery and development of microbial-derived lanthipeptides.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Infectious Diseases
Xiao-Xin Xue, Lin Chen, Man-Cheng Tang
Summary: In this study, a biosynthetic gene cluster from Neosartorya pseudofischeri was discovered, and the biosynthetic pathway of pseudofisnins was elucidated. The methyltransferase PseC in the pathway was also characterized.
Article
Biotechnology & Applied Microbiology
Laura Prado-Alonso, Ignacio Perez-Victoria, Monica G. Malmierca, Ignacio Montero, Elisa Rioja-Blanco, Jesus Martin, Fernando Reyes, Carmen Mendez, Jose A. Salas, Carlos Olano
Summary: Genome mining has revealed the biosynthetic potential of actinomycetes and led to the discovery of novel halogenated bioactive compounds. In this study, a screening for halogenase coding genes in Streptomyces strains isolated from fungus-growing ants identified six genes. Mutants were constructed to study the biosynthetic gene clusters and a novel family of halogenated compounds, named colibrimycins, were identified in Streptomyces sp. strain CS147.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Chemistry, Organic
Romina Schnegotzki, Vincent Wiebach, Marina Sanchez-Hidalgo, Marcel Tietzmann, Andreas B. zur Bonsen, Olga Genilloud, Roderich D. Suessmuth
Summary: Phenylglycines are crucial components in the synthesis of non-ribosomally synthesized peptides. The cyclodepsipeptide cochinmicin I, which contains dihydroxyphenylglycine, acts as an endothelin receptor antagonist. In this study, we accomplished the total synthesis of cochinmicin I and its non-natural derivative cochinmicin VI. Additionally, we identified and assigned the gene cluster responsible for cochinmicin biosynthesis, which encodes a non-ribosomal peptide synthetase.
Article
Microbiology
Lucija Slemc, Jernej Jakse, Alessandro Filisetti, Damir Baranasic, Antonio Rodriguez-Garcia, Francesco Del Carratore, Stefano Maria Marino, Jurica Zucko, Antonio Starcevic, Martin Sala, Mercedes Perez-Bonilla, Marina Sanchez-Hidalgo, Ignacio Gonzalez, Fernando Reyes, Olga Genilloud, Vicki Springthorpe, Dusan Goranovic, Gregor Kosec, Gavin H. Thomas, Davide De Lucrezia, Hrvoje Petkovic, Miha Tome
Summary: Streptomyces rimosus ATCC 10970 is a challenging bacterium to assemble due to its long repeats, high GC content, and a single giant linear plasmid (GLP). In this study, a hybrid sequencing approach was used to generate a high-quality reference genome for this industrially important bacterium. The GLP of the parent strain ATCC 10970 and two semi-industrial progenitor strains were sequenced, revealing rearrangements accompanied by transposase genes. This study sheds light on the role of transposases in genome plasticity and provides valuable information on secondary metabolite biosynthetic pathways.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biochemistry & Molecular Biology
Haoqian Liang, Isaiah J. Lopez, Marina Sanchez-Hidalgo, Olga Genilloud, Wilfred A. van der Donk
Summary: In this study, the in vitro biosynthesis process of class V lanthipeptide cacaoidin was reconstituted, and a novel dehydration enzyme CaoK and effector protein CaoY were discovered to play critical roles. Through mutagenesis studies and structure prediction, the importance of hydrophobic interactions in enzyme-substrate recognition was revealed.
ACS CHEMICAL BIOLOGY
(2022)
Article
Cell Biology
Lorena Cuervo, Carmen Mendez, Jose A. Salas, Carlos Olano, Monica G. Malmierca
Summary: This study highlights the importance of discovering new therapeutic alternatives, especially natural compounds that can be used to treat multiresistant pathogens and emerging diseases. The research finds that volatile compounds (VOCs) have the ability to activate biosynthetic pathways of bioactive compounds in Actinomycetes, leading to increased antibiotic production and synthesis of new VOCs. The results demonstrate a novel strategy to exploit the metabolic potential of Actinomycetes and emphasize the significance of studying interactions between different microorganisms sharing the same ecological niche.
Article
Biotechnology & Applied Microbiology
Suhui Ye, Giovanni Ballin, Ignacio Perez-Victoria, Alfredo F. Brana, Jesus Martin, Fernando Reyes, Jose A. Salas, Carmen Mendez
Summary: By combining different enzymes, the biosynthesis pathways of two polyketide alkaloids were modified, resulting in the production of new compounds with novel scaffolds, one of which exhibited improved antibiotic activity.
MICROBIAL BIOTECHNOLOGY
(2022)
Article
Microbiology
Marina Sanchez-Hidalgo, Maria Jesus Garcia, Ignacio Gonzalez, Daniel Oves-Costales, Olga Genilloud
Summary: In this study, a strain of Kribbella sp. CA-293567 was found to produce sandramycin and kribbellichelins A-B, which are new secondary metabolites. The complete genome sequencing and in silico identification of biosynthetic gene clusters were performed, focusing on the pathways encoding these compounds. A comparative analysis of the biosynthetic potential of 38 publicly available genomes from Kribbella strains was also presented.
Article
Biochemistry & Molecular Biology
Suhui Ye, Brian Molloy, Ignacio Perez-Victoria, Ignacio Montero, Alfredo F. Brana, Carlos Olano, Sonia Arca, Jesus Martin, Fernando Reyes, Jose A. Salas, Carmen Mendez
Summary: Genome mining using bioinformatics tools allowed for uncovering hidden biosynthesis gene clusters, while an alternative approach involving the analysis of Streptomyces Antibiotic Regulatory Proteins (SARP) encoding genes was used to identify cryptic gene clusters. This strategy led to the discovery of the new ahb cluster in Streptomyces argillaceus and the identification of ahbamycins as a new family of metabolites with antibiotic and antitumor activity. Further investigation revealed a hybrid compound, AHB18, produced through metabolic crosstalk between the ahb and argimycin P pathways. This finding opens up possibilities for generating new compounds through combinatorial biosynthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Lorena Cuervo, Monica G. Malmierca, Raul Garcia-Salcedo, Carmen Mendez, Jose A. Salas, Carlos Olano, Ana Ceniceros
Summary: The search for novel bioactive compounds to overcome resistance to current therapeutics has become crucial. Streptomyces spp. are a major source of bioactive compounds used in medicine. In this study, global transcriptional regulators and housekeeping genes known to enhance secondary metabolite production in Streptomyces coelicolor were cloned and expressed in different strains. The recombinant plasmids were also inserted into Streptomyces strains with enhanced secondary metabolism. Media with varied carbon and nitrogen sources were used, and the strains' metabolite production was analyzed. The study demonstrated the overproduction and activation of known metabolites and the potential for manipulating Streptomyces metabolism and exploring their wide range of secondary metabolites.
Article
Biochemistry & Molecular Biology
Ana Ceniceros, Librada Canedo, Carmen Mendez, Carlos Olano, Carmen Schleissner, Carmen Cuevas, Fernando de la Calle, Jose A. Salas
Summary: Three novel lipopeptides were isolated from a marine sediment-derived Streptomyces tuirus and they exhibited cytotoxic activity against human cancer cell lines. The biosynthesis of these lipopeptides was found to be dependent on a gene cluster.
Article
Microbiology
Celia Bautista-Crescencio, Arturo Casimiro-Ramos, M. Jonathan Fragoso-Vazquez, Jose Correa-Basurto, Carlos Olano, Cesar Hernandez-Rodriguez, Lourdes Villa-Tanaca
Summary: There is an urgent need to develop new antifungals due to the increasing prevalence of multidrug-resistant fungal infections and the recent emergence of COVID-19-associated candidiasis. In this study, antifungal metabolites produced by Streptomyces albidoflavus Q were investigated, and two secondary metabolites were found to have a good inhibitory effect on Candida glabrata, which may be potential candidates for treating fungal infections.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biotechnology & Applied Microbiology
Marcin Wolanski, Michal Krawiec, Paul N. Schwarz, Evi Stegmann, Wolfgang Wohlleben, Anina Buchmann, Harald Gross, Michael Eitel, Pierre Koch, Alma Botas, Carmen Mendez, Luz Elena Nunez, Francisco Moris, Jesus Cortes, Jolanta Zakrzewska-Czerwinska
Summary: LysRNt was discovered as a novel regulator of the Bra-BGC, negatively affecting the production of brasilicardin congeners in a heterologous host. Through in vivo and in vitro experiments, gene promoters controlled by LysRNt within the Bra-BGC were identified. Metabolites related to the pathway and their chemical analogs were found to interact with LysRNt, influencing its DNA-binding activity.
ENGINEERING IN LIFE SCIENCES
(2021)
