Topics and Trends in Most Cited Microbial Natural Products and Biosynthesis Papers

Ranked by citations 18 months after publication

Class of 2026 (Papers Published in 2024)

What topics and trends defined most-cited Microbial Natural Products and Biosynthesis research in the Class of 2026?

The Class of 2026 in Microbial Natural Products and Biosynthesis reflects a shift from pure genome mining toward functional validation. While biosynthetic gene clusters remain foundational, research is increasingly focusing on heterologous expression, pathway engineering, and data-driven approaches using natural product databases.

See details ↓

Updated September 14, 2026

At a glance

Field
Microbial Natural Products and Biosynthesis
Cohort label
Class of 2026 (2024 publications)
Papers analyzed
4,273
Papers ranked
20
Top topics in ranked papers
Biosynthetic gene clusters, heterologous expression, cytochrome P450, RiPPs
Publication window
Jan 1, 2024 – Dec 31, 2024
Eligibility
Research articles; reviews excluded
Citation window
18 months post-publication
18m citation range
25–184
Data source
OpenAlex · Retrieved September 2026
License
CC BY 4.0

Rankings

20 papers ranked by 18-month citation count

#1 of 4,273
18418m citations

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration

Mitja M Zdouc et al.Nucleic Acids Research202410.1093/nar/gkae1115

Mitja M ZdoucWageningen University & Research, Netherlands

biosynthetic gene clusternatural productsMIBiG databaseMinimum Information about a Biosynthetic Gene clusterMIBiG data standardcommunity annotationautomated data validationpeer-reviewing modelmachine-readable dataBGC curationrolling release modelsubmission portaldata quality
Badge
#2 of 4,273
10418m citations

COCONUT 2.0: a comprehensive overhaul and curation of the collection of open natural products database

Venkata Chandrasekhar et al.Nucleic Acids Research202410.1093/nar/gkae1063

Christoph SteinbeckFriedrich Schiller University Jena, Germany

COCONUT databasenatural product databaseschemical structure aggregationnatural product curationstructure searchsubstructure searchsimilarity searchnatural product synonymsspecies occurrence datageographic origin metadataliterature referencesSDF formatCSV formatdatabase dumpopen-source web applicationuser data submissioncommunity curation
Badge
#3 of 4,273
10318m citations

Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III

Bin Jiang, Lei Gao, Haijun Wang, Yaping Sun et al.Science202410.1126/science.adj3484

Bin Jiang, Lei Gao, Haijun Wang, Ya‐Ping Sun, Huan Wang, Xiaoguang Lei, Jianbin YanAgricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, China

paclitaxelbaccatin IIITaxus maireitaxane oxetanase 1TOT1cytochrome P450oxetane ring formationoxidative rearrangementT9αH1C9 position oxidationtaxusin biosynthesis pathwayditerpenoidphenylisoserinoyl side chainheterologous expressiontobaccopaclitaxel biosynthesis
Badge
#5 of 4,273
7818m citations

The Natural Products Atlas 3.0: extending the database of microbially derived natural products

Ella F Poynton et al.Nucleic Acids Research202410.1093/nar/gkae1093

Roger G. LiningtonSimon Fraser University, Canada

natural product databasesnatural productsbiosynthetic ontologychemical ontologycompound classesstructure searchchemical diversity visualizationStructure revisionsproducing organism taxonomyinteractive dashboardsdatabase curationcross-linking data resources
Badge
#6 of 4,273
7318m citations

Complete biosynthesis of QS-21 in engineered yeast

Yuzhong Liu et al.Nature202410.1038/s41586-024-07345-9

Jay D. KeaslingUniversity of California, Berkeley, United States

QS-21vaccine adjuvantsaponinChilean soapbark treeyeast biosynthesispathway engineeringheterologous expressionterpene synthasecytochrome P450nucleotide sugar synthasesglycosyltransferasescoenzyme A ligaseacyltransferasespolyketide synthasesubcellular compartmentalizationendoplasmic reticulumsubstrate promiscuitystructural analoguesstructure-activity relationshipsmetabolic flux tuning
Badge
#7 of 4,273
6418m citations

Complete biosynthesis of the potent vaccine adjuvant QS-21

Laetitia B B Martin et al.Nature Chemical Biology202410.1038/s41589-023-01538-5

Anne OsbournJohn Innes Centre, United Kingdom

QS-21vaccine adjuvantChilean soapbark treeglycosylated triterpene scaffold18-carbon acyl chainT cell proliferationacyl chain biosynthesisheterologous expressiontobacco expression system20-step biosynthetic pathwaytriterpene glycosideimmunostimulant activitystructure-activity relationshipsbioengineering vaccine adjuvantssaponin biosynthesis
Badge
#8 of 4,273
6418m citations

Natural Products Have Increased Rates of Clinical Trial Success throughout the Drug Development Process

Daniel Domingo-Fernández et al.Journal of Natural Products202410.1021/acs.jnatprod.4c00581

Daniel Domingo‐FernándézEnveda Biosciences, United States

natural productsclinical trial success ratedrug development processNP-derived compoundssynthetic compoundspatent applicationsclinical trial phases I to IIIin vitro toxicity studiesin silico toxicity studiesdrug approvalearly-stage drug discoverylate-stage drug discoverycompound toxicity comparisonNP-based drug development
Badge
#9 of 4,273
5618m citations

Evolution-inspired engineering of nonribosomal peptide synthetases

Kenan A J Bozhüyük, Leonard Präve, Carsten Kegler, Leonie Schenk et al.Science202410.1126/science.adg4320

Kenan A. J. Bozhüyük, Leonard Präve, Carsten Kegler, Leonie Schenk, Helge B. BodeMax Planck Institute for Terrestrial Microbiology, Germany

nonribosomal peptide synthetasesNRPS engineeringphylogenetic analysisThiolation domainrecombination siteseXchange Unit between T domainsnatural productsmegasynthetasesassembly line biosynthesisGC contentextender unit specificityproteasome inhibitorNRPS fragment assemblymodule exchangeevolution-inspired design
Badge
#10 of 4,273
4218m citations

Reconstitution of early paclitaxel biosynthetic network

Jack Chun-Ting Liu et al.Nature Communications202410.1038/s41467-024-45574-8

Elizabeth S. SattelyStanford University, United States

paclitaxel biosynthesistaxadiene 5α-hydroxylaseT5αHcytochrome P450heterologous expressionover-oxidationtaxadien-5α-olNicotianapromoter strength tuningsix step biosynthetic pathwaymetabolic networkTaxus genespaclitaxel intermediatesyew tree
Badge
#11 of 4,273
3918m citations

Evolution-guided engineering of trans -acyltransferase polyketide synthases

Mathijs F. J. Mabesoone et al.Science202410.1126/science.adj7621

Mathijs F. J. Mabesoone, Stefan Leopold‐Messer, Hannah A. Minas, Jörn PielEidgenössische Technische Hochschule (ETH) Zürich, Switzerland

trans-acyltransferase polyketide synthasescis-acyltransferase PKSsmodular polyketide synthasesPKS modulesCo-evolution analysishybrid PKSsmodule insertionmodule deletionPKS engineeringpolyketide diversificationdesigner polyketidesnatural productsassembly line enzymescoevolution-guided engineeringmodule exchange sitepathway engineering
Badge
#12 of 4,273
3918m citations

Cell-free biosynthesis and engineering of ribosomally synthesized lanthipeptides

Wan-Qiu Liu, Xiangyang Ji et al.Nature Communications202410.1038/s41467-024-48726-y

Yifan Liu, Shengjie Ling, Michael C. Jewett, Jian LiShanghaiTech University, China

ribosomally synthesized and post-translationally modified peptideslanthipeptidescell-free biosynthesisUniBioCat systemsalivaricin Bde novo biosynthesisProtease deletionantimicrobial activity screeninglanthipeptide variantsheterologous expressionpathway reconstitutionRiPP biosynthetic gene clustersnatural product discovery
Badge
#13 of 4,273
3518m citations

Green synthesis of zinc oxide nanoparticles (ZnO-NPs) by Streptomyces baarnensis and its active metabolite (Ka): a promising combination against multidrug-resistant ESKAPE pathogens and cytotoxicity

Mohamed H Kalaba et al.BMC Microbiology202410.1186/s12866-024-03392-4

Gamal M. El-SherbinyAl-Azhar University, Egypt

ZnO-NPs biosynthesisStreptomyces baarnensis MH-1339-Ethyl-1,4,6,9,10-pentahydroxy-7,8,9,10-tetrahydrotetracene-5,12-dioneKa compoundzinc sulfate precursorHR-TEM characterizationcheckerboard microdilutionfractional inhibitory concentration indexKa-ZnO-NPs nanoemulsionMethicillin-resistant Staphylococcus aureusKlebsiella pneumoniaeESKAPE pathogenskilling kinetic assaysynergistic antibacterial activitypolydispersity indexVERO cell cytotoxicitybactericidal effectnanoemulsion formulationMultidrug-resistant bacteriaX-ray crystal structure
Badge
#14 of 4,273
3218m citations

Effectiveness of molecular fingerprints for exploring the chemical space of natural products

Davide Boldini et al.Journal of Cheminformatics202410.1186/s13321-024-00830-3

Davide BoldiniTechnical University of Munich, Germany

natural productsmolecular fingerprintschemical space explorationCOCONUT databaseCMNPD databasebioactivity predictionsp3-hybridized carbonsstereocenterspairwise similaritycheminformaticsfingerprint performance benchmarkingstructural encodingdrug-like compoundsmarine natural products
Badge
#15 of 4,273
3118m citations

BGC Atlas: a web resource for exploring the global chemical diversity encoded in bacterial genomes

Caner Bağcı et al.Nucleic Acids Research202410.1093/nar/gkae953

Nadine ZiemertUniversity of Tübingen, Germany

biosynthetic gene clusternatural productsmetagenomicsgene cluster familiesGCFsBGC AtlasMGnifyribosomally synthesized and post-translationally modified peptidesenvironmental specificityBGC clusteringmetadata-aware explorationbacterial genomeschemical diversitybiosynthetic potentialmicrobial communitiesenvironmental samples
Badge
#16 of 4,273
3018m citations

Advanced technologies targeting isolation and characterization of natural products

Shu-Hui Dong et al.TrAC Trends in Analytical Chemistry202410.1016/j.trac.2024.117711

Xiao‐Xiao Huang, Shao‐Jiang SongEngineering Research Center of Natural Medicine Active Molecule Research & Development, China

natural productsisolation techniquescharacterization methodsadvanced technologiesstructural characterizationbioactive compoundsmass spectrometrynuclear magnetic resonance spectroscopychromatographic separationmetabolomicshigh-throughput screeningdereplication strategiespurification workflows
Badge
#17 of 4,273
2818m citations

A widespread family of ribosomal peptide metallophores involved in bacterial adaptation to metal stress

Laura Leprevost, Sophie Jünger, Guy Lippens, Rudy Antoine, Séverine Zirah, Svetlana Dubiley, Yanyan Li, Françoise Jacob-Dubuisson et al.Proceedings of the National Academy of Sciences202410.1073/pnas.2408304121

Laura Leprévost, Sophie Jünger, Guy Lippens, Rudy Antoine, Séverine Zirah, Svetlana Dubiley, Yanyan Li, Françoise Jacob‐DubuissonUniv. Lille, France

bufferinsribosomally synthesized and post-translationally modified peptidesMultinuclear non-heme iron-dependent oxidative enzymesDUF6925-thiooxazolesthiooxazole heterocyclesDUF2063 familyCaulobacter vibrioidesN-terminal Sec signal peptideSec pathwaycopper homeostasiscopper stressmetallophoresmetal-bindingPost-translational modificationsbiosynthetic gene cluster
Badge
#19 of 4,273
2718m citations

MetOrigin 2.0: Advancing the discovery of microbial metabolites and their origins

Gang Yu et al.iMeta202410.1002/imt2.246

Junfen Fu, Yan NiChildren's Hospital Zhejiang University School of Medicine, China

MetOriginnatural productsmicrobiome-metabolome interplayquick search moduleorthology analysis modulemediation analysis modulemetabolic enzyme genesbacteria-metabolite associationscausal relationshipsmediating role of metabolitesKEGGHMDBBIGGChEBIFoodDBDrugBankT3DBmetabolite source organism
Badge
#20 of 4,273
2518m citations

A treasure trove of 1034 actinomycete genomes

Tue Sparholt Jørgensen et al.Nucleic Acids Research202410.1093/nar/gkae523

Tilmann WeberTechnical University of Denmark, Denmark

Actinomycetiafilamentous Actinobacteriacomplete genomesbiosynthetic gene clusterStreptomycesNBC culture collectionlinear chromosometerminal inverted repeatstrans-acyltransferase polyketide synthasesCore genessyntenychromosome-level assembliesnatural productsduplicate core genes
Badge

Dominant research themes and year-over-year shifts in Microbial Natural Products and Biosynthesis

What Topics Define the Class of 2026?

The Class of 2026 is characterized by a strong emphasis on the functional characterization and optimization of microbial natural products. The landscape is dominated by research on **biosynthetic gene clusters** (present in 23.9% of top papers) and **heterologous expression** (21.7%), underscoring the critical need to activate and produce cryptic metabolites. Enzymatic mechanisms and tailored modifications also feature prominently, with **cytochrome P450** enzymes (13.0%) and **ribosomally synthesized and post-translationally modified peptides (RiPPs)** (13.0%) representing key areas of structural diversification. Furthermore, the robust presence of **metabolic engineering** (10.9%) and **nonribosomal peptide synthetases** (6.5%) indicates a persistent focus on rewiring cellular metabolism and deciphering complex modular assembly lines to discover novel bioactive compounds.

Leading research themes
Leading research themes

How Did Topics Shift from the Class of 2025 to the Class of 2026?

A compelling shift is underway from initial computational discovery to active downstream biosynthesis. The most striking decline was observed in **genome mining**, which fell precipitously from 27.1% to just 6.5%. Similarly, mentions of **biosynthetic gene clusters** contracted from 39.6% to 23.9%. Conversely, researchers are increasingly prioritizing experimental validation and production. **Heterologous expression** expanded 1.3-fold to 21.7%, while **pathway engineering** jumped more than 3-fold to 6.5%. The data also highlights a surge in computational infrastructure supporting this work: topics such as **natural product databases**, the **COCONUT database**, and **co-evolution analysis** emerged strongly in 2024 after being absent among top papers in the previous cohort, reflecting a maturation of the field toward more integrated, data-driven synthetic biology.

How topics shifted year over year
How topics shifted year over year
Methodology

PRI identifies high-impact research using a transparent, topic-agnostic framework applied consistently across scientific domains. Bibliographic records are drawn from OpenAlex, including publication dates, citation relationships, and document types.

This ranking covers the Class of 2026 cohort: journal articles published in 2024. Reviews and other non-article document types are excluded to ensure comparability.

Research impact is quantified with an 18-month post-publication citation window—the number of citing works published within 18 months of each paper's publication date. This metric captures early impact while controlling for publication age.

An LLM-based relevance classifier then reviews each candidate's title and abstract to confirm substantive alignment with the target domain. Only papers classified as relevant appear in the final ranking.

Zheng Su, Tinsley Li, Thematic Shifts in Early-High-Impact Cancer Genomics and Diagnostics Research: A Bibliometric and Semantic Analysis. bioRxiv 2026.07.04.736459; doi: https://doi.org/10.64898/2026.07.04.736459

Full methodologyGitHubbioRxiv preprint

Cite this ranking

Pepkio Research Index (PRI). Topics and Trends in Most Cited Microbial Natural Products and Biosynthesis Papers, Class of 2026. https://pri.pepkio.com/top-papers/microbial-natural-products-and-biosynthesis/2026. Accessed 2026-10-24.

Methodology
Zheng Su, Tinsley Li, Thematic Shifts in Early-High-Impact Cancer Genomics and Diagnostics Research: A Bibliometric and Semantic Analysis. bioRxiv 2026.07.04.736459; doi: https://doi.org/10.64898/2026.07.04.736459