Article
Biotechnology & Applied Microbiology
Jake Wilson, Jerry Cui, Toshiki Nakao, Happy Kwok, Yeying Zhang, Chase M. Kayrouz, Tiffany M. Pham, Hannah Roodhouse, Kou-San Ju
Summary: Phosphonate natural products have inhibitory activities and are used as antibiotics and pesticides. We found a new phosphonate compound produced by Bacillus velezensis, which exhibits broad-spectrum antibacterial activity against various pathogens. This discovery expands our knowledge of phosphonate metabolism and highlights the importance of exploring underexplored microbial taxa in natural product discovery.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Zhijie Zhao, Guiyun Zhao, Yi Chai, Wei Li, Kaihui Song, Wenbin Zhao, Hairong Li, Miaolian Wu, Zhan Zhou, Yi-Ling Du
Summary: In the current postgenomic era, sequence-driven approaches for natural product discovery are becoming popular.We developed an effective genome mining strategy for targeted discovery of microbial metabolites with antitumor activities.Our research provides a new genome mining strategy for efficient discovery of antitumor agents acting through DNA intercalation.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Linda Sukmarini
Summary: Natural products are optimized as drug-like molecules and have been a consistently successful source of drugs. Recent advancements in unconventional secondary metabolomics techniques have accelerated the discovery of new lead structures from natural sources by utilizing a deeper understanding of biosynthetic pathways and advancements in analytical instrumentation.
Review
Pharmacology & Pharmacy
Autumn Arnold, Jeremie Alexander, Gary Liu, Jonathan M. Stokes
Summary: Machine learning is proving to be valuable at various stages of the microbial natural product drug discovery pipeline, including genome mining, dereplication, and biological target prediction. It has the ability to model complex datasets and generalize to novel chemical and sequence space, thus overcoming the challenges associated with conventional discovery processes.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Joachim J. Hug, Nicolas A. Frank, Christine Walt, Petra Senica, Fabian Panter, Rolf Mueller
Summary: Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a diverse group of natural products with intriguing modifications, such as the biarylitides. Recent genomic analyses have shown that the biosynthesis of biarylitides only requires a pentapeptide precursor and a modifying cytochrome-P450-dependent enzyme. This discovery expands the biosynthetic scope of RiPPs and highlights the unique biochemistry found in myxobacteria.
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
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)
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
Agriculture, Multidisciplinary
Wenqin Li, Yi Ding, Huitang Qi, Tian Liu, Qing Yang
Summary: The study found that several phytochemicals can inhibit multiple insect chitinolytic enzymes simultaneously, with predicted interactions with key residues and good insecticidal activity. This research provides a new approach for using a multitarget high-throughput screening strategy to discover natural products as insecticide leads.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Max Cruesemann
Summary: Traditional natural product discovery approaches are limited in terms of dereplication, but recent advances in mass spectrometry, sequencing, and bioinformatics have provided important tools for accelerating and rationalizing natural product discovery. By utilizing signature-based or correlation-based mass spectrometry genome mining approaches, metabolomic and genomic information can be rapidly linked.
Article
Biochemistry & Molecular Biology
Shefali Arora, Sukanya Chettri, Versha Percha, Deepak Kumar, Mamta Latwal
Summary: Nature is a rich source of medicinal substances, and researchers have been inspired to explore natural product-inspired medicine due to the heterogeneity and unique characteristics of natural products. Artificial intelligence (AI) has been used to enhance natural product-based drug discovery, allowing for innovative molecular design and lead discovery. Machine learning models have been developed to quickly synthesize mimetics of natural product templates. The use of computer-assisted technology in creating novel natural product mimetics provides a feasible strategy for obtaining natural products with defined bio-activities. AI's high hit rate is crucial for improving trial patterns and formulating advanced medicinal applications for natural products in a targeted manner.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Mary M. LeClair, Zacharie A. Maw, Alyssa L. Grunwald, Joshua R. Kelly, Bradley A. Haltli, Russell G. Kerr, Christopher Cartmell
Summary: Levesquamide A is an anti-tubercular natural product, and additional members of the levesquamide family have been identified using GNPS. Levesquamide B has been structurally elucidated, while the structures of levesquamide C, D, and the other three levesquamides remain ambiguous.
Article
Microbiology
Paton Vuong, Daniel J. Lim, Daniel V. Murphy, Michael J. Wise, Andrew S. Whiteley, Parwinder Kaur
Summary: By mining global genome repositories for PhaC enzymes, potential PHA-producing bacteria and archaea were identified, including those from unique environmental niches that could enhance PHA production. This in silico study provides valuable insights for future bioprospecting efforts aimed at diversifying and improving PHA production systems.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Rajkumari Mazumdar, Kangkon Saikia, Debajit Thakur
Summary: This study explored the potential of actinomycetia as a source of bioactive compounds with antimicrobial properties against multi-drug resistant clinical pathogens. 19 isolates out of 65 actinomycetia exhibited significant antimicrobial activity, with Streptomyces being the most dominant genus. Seventeen isolates tested positive for antibiotic biosynthetic genes, specifically PKS-II and NRPSs. Three strains of actinomycetia demonstrated the most potent antimicrobial activity and analysis revealed diverse bioactive compounds and secondary metabolite biosynthetic gene clusters, indicating their high therapeutic potential.
Review
Chemistry, Medicinal
Jessie James Limlingan Malit, Hiu Yu Cherie Leung, Pei-Yuan Qian
Summary: Large-scale genome-mining analyses have identified numerous cryptic biosynthetic gene clusters (BGCs) as a valuable source of novel bioactive natural products. Effective strategies and computational methods are essential for selecting appropriate BGCs for further characterization and production of natural products. Studies have successfully produced compounds with high chemical novelty, novel biosynthesis pathways, and potent bioactivities by prioritizing candidate BGCs based on different logics such as detection of resistance genes, phylogenomics analysis, and targeting specific chemical structures.