Natural product drug discovery in the artificial intelligence era

Chemical Science, Год журнала: 2021, Номер 13(6), С. 1526 - 1546

Опубликована: Дек. 13, 2021

Natural products (NPs) are primarily recognized as privileged structures to interact with protein drug targets.

Язык: Английский

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Designing Microbial Cell Factories for the Production of Chemicals

JACS Au, Год журнала: 2022, Номер 2(8), С. 1781 - 1799

Опубликована: Авг. 4, 2022

The sustainable production of chemicals from renewable, nonedible biomass has emerged as an essential alternative to address pressing environmental issues arising our heavy dependence on fossil resources. Microbial cell factories are engineered microorganisms harboring biosynthetic pathways streamlined produce interests renewable carbon sources. for the can be defined into three categories with reference microbial host selected engineering: native-existing pathways, nonnative-existing and nonnative-created pathways. Recent trends in leveraging discovering designing de novo (as pathways) discussed this Perspective. We highlight key approaches successful case studies that exemplify these concepts. Once designed constructed factory, systems metabolic engineering strategies used improve performance strain meet industrial standards. In second part Perspective, current design tools eye toward future. Finally, we survey future challenges need addressed advance chemicals.

Язык: Английский

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Advanced Methods for Natural Products Discovery: Bioactivity Screening, Dereplication, Metabolomics Profiling, Genomic Sequencing, Databases and Informatic Tools, and Structure Elucidation

Marine Drugs, Год журнала: 2023, Номер 21(5), С. 308 - 308

Опубликована: Май 19, 2023

Natural Products (NP) are essential for the discovery of novel drugs and products numerous biotechnological applications. The NP process is expensive time-consuming, having as major hurdles dereplication (early identification known compounds) structure elucidation, particularly determination absolute configuration metabolites with stereogenic centers. This review comprehensively focuses on recent technological instrumental advances, highlighting development methods that alleviate these obstacles, paving way accelerating towards Herein, we emphasize most innovative high-throughput tools advancing bioactivity screening, chemical analysis, dereplication, metabolite profiling, metabolomics, genome sequencing and/or genomics approaches, databases, bioinformatics, chemoinformatics, three-dimensional elucidation.

Язык: Английский

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Medicinal plants meet modern biodiversity science

Current Biology, Год журнала: 2024, Номер 34(4), С. R158 - R173

Опубликована: Фев. 1, 2024

Plants have been an essential source of human medicine for millennia. In this review, we argue that a holistic, interdisciplinary approach to the study medicinal plants combines methods and insights from three key disciplines - evolutionary ecology, molecular biology/biochemistry, ethnopharmacology is poised facilitate new breakthroughs in science, including pharmacological discoveries rapid advancements health well-being. Such research leverages data spanning space, time, species associated with plant evolution, genomics, metabolomic trait diversity, all which build heavily on traditional Indigenous knowledge. contrasts sharply most well-funded successful during last half-century, which, despite notable advancements, has greatly oversimplified dynamic relationships between humans, kept hidden larger narratives about these relationships, overlooked potentially important into life-saving medicines. We suggest people should be viewed as partners whose relationship involves complicated poorly explored set (socio-)ecological interactions not only domestication but also commensalisms mutualisms. short, are just chemical factories extraction exploitation. Rather, they may symbiotic shaped modern societies, improved health, extended lifespans.

Язык: Английский

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Metabolomics and genomics in natural products research: complementary tools for targeting new chemical entities

Natural Product Reports, Год журнала: 2021, Номер 38(11), С. 2041 - 2065

Опубликована: Янв. 1, 2021

Here we provide a comprehensive guide for studying natural product biosynthesis using genomics, metabolomics, and their integrated datasets. We emphasize strategies critical outlook on remaining challenges in the field.

Язык: Английский

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Biosynthesis, evolution and ecology of microbial terpenoids

Natural Product Reports, Год журнала: 2021, Номер 39(2), С. 249 - 272

Опубликована: Окт. 9, 2021

Terpenoids have diverse bioecological roles in all kingdoms of life. Here we discuss the evolution and ecological functions microbial terpenoids their possible applications.

Язык: Английский

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Actinobacteria From Desert: Diversity and Biotechnological Applications

Frontiers in Microbiology, Год журнала: 2021, Номер 12

Опубликована: Дек. 9, 2021

Deserts, as an unexplored extreme ecosystem, are known to harbor diverse actinobacteria with biotechnological potential. Both multidrug-resistant (MDR) pathogens and environmental issues have sharply raised the emerging demand for functional actinobacteria. From 2000 2021, 129 new species been continuously reported from 35 deserts worldwide. The two largest numbers of members genera Streptomyces Geodermatophilus , followed by other extremophilic strains such alkaliphiles, halotolerant species, thermophiles, psychrotolerant species. Improved isolation strategies recovery culturable unculturable desert crucial exploration their diversity offer a better understanding survival mechanisms under stresses. main bioprospecting processes involve target on selective media incubation selection representatives plates further investigations. Bioactive compounds obtained being explored potential, especially in medicine. To date, there more than 50 novel discovered these gifted potential antimicrobial activities, including anti-MDR anti-inflammatory, antivirus, antifungal, antiallergic, antibacterial, antitumor, cytotoxic activities. A range plant growth-promoting abilities inspired great interest agricultural In addition, several degradative, oxidative, enzymes can be applied industry environment. This review aims provide comprehensive overview environments remarkable source while rich offers underexplored resource exploitations.

Язык: Английский

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Advancements in capturing and mining mass spectrometry data are transforming natural products research

Natural Product Reports, Год журнала: 2021, Номер 38(11), С. 2066 - 2082

Опубликована: Янв. 1, 2021

This review covers the current and potential use of mass spectrometry-based metabolomics data mining in natural products. Public data, metadata, databases analysis tools are critical. The value success rely on community participation.

Язык: Английский

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The Natural Product Domain Seeker version 2 (NaPDoS2) webtool relates ketosynthase phylogeny to biosynthetic function

Journal of Biological Chemistry, Год журнала: 2022, Номер 298(10), С. 102480 - 102480

Опубликована: Сен. 12, 2022

The Natural Product Domain Seeker (NaPDoS) webtool detects and classifies ketosynthase (KS) condensation domains from genomic, metagenomic, amplicon sequence data. Unlike other tools, a phylogeny-based classification scheme is used to make broader predictions about the polyketide synthase (PKS) nonribosomal peptide synthetase (NRPS) genes in which these are found. NaPDoS particularly useful for analysis of incomplete biosynthetic or gene clusters, as often observed poorly assembled genomes metagenomes, when loci not clustered, eukaryotic genomes. To help support growing interest sequence-based analyses natural product diversity, here we introduce version 2 webtool, NaPDoS2, available at http://napdos.ucsd.edu/napdos2. This update includes addition 1417 KS sequences, representing major expansion taxonomic functional diversity represented database. now recognizes 41 class subclass assignments, including new type II PKS subclasses. Workflow modifications accelerate run times, allowing larger datasets be analyzed. In addition, default parameters were established using statistical validation tests maximize detection accuracy while minimizing false positives. We further demonstrate applications NaPDoS2 assess potential PCR datasets. These examples illustrate how can predict detect involved biosynthesis specific structure classes mechanisms.

Язык: Английский

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Structural advances toward understanding the catalytic activity and conformational dynamics of modular nonribosomal peptide synthetases

Natural Product Reports, Год журнала: 2023, Номер 40(9), С. 1550 - 1582

Опубликована: Янв. 1, 2023

Nonribosomal peptide synthetases use a modular architecture to catalyze production of natural products. Structural studies provide insights into the multidomain organization as well structural basis catalytic domain activity.

Язык: Английский

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