About

Modern drug discovery and today's pharmacopeia is largely benefited from nature. More than 50% of approved drugs are natural products or natural product derivatives. It is estimated that there are about a million natural products have been isolated and many of them have been subjected to experimental assays to evaluate quantitative biological activities. By manually collecting and integrating these valuable data from individual literatures into a centralized database, the Natural Product Activity and Species Source Database (NPASS) has served as one of a leading data source for the NP research community since its first version release in 2017 (Nature Reviews Drug Discovery 22.11 (2023): 895–916).

NPASS has demonstrated a substantial influence on the field of natural product research since its initial release. The following examples illustrate this impact:

• Athina Gavriilidou et al. analyzed the biosynthetic diversity and NP discovery hotspots to guide NP research trends (Nature Microbiology, 7:726–735, 2022).
• Michael A. Skinnider et al. developed artificial intelligence algorithms for molecular AI design (Nature Machine Intelligence, 3:759–770, 2021).
• Laura Holzmeyer et al. revealed hidden relationships between phylogenetic, spatial, and bioactivity patterns of plant-derived NPs (PNAS, 117(22):12444–12451, 2020).
• PubChem 2025 update incorporated NPASS data to enhance coverage of bioactive natural compounds and their species origins (Nucleic Acids Research 53.D1 (2025): D1516–D1525).

Since 2018, a large number of new NPs have been found and biologically evaluated against a broad of biological targets by the research community, to better benefit the NP research community, we updated NPASS database to deposit more data points and more information layers of NP in the new version (v3.0). The NPASS database in the current version (V3.0) provides 204,023 unique natural products isolated from 48,940 source organisms and together with 1,048,756 activity records on 8,764 targets. Major changes in NPASS-v3.0 were summarized in the below table:

We also compare NPASS with several popular NP databases:

❖ Symbiosis as a rich source for natural product drug discovery

Symbiosis represents a powerful and underexplored resource in the search for novel natural products. Symbionts—microorganisms that live in close association with host organisms—significantly expand the chemical space available for therapeutic development. These relationships, which can be commensal, mutualistic, or parasitic, are often mediated and regulated by specialized natural products that facilitate communication, defense, and metabolic cooperation within the symbiotic system.

The coevolution of microbial symbionts with their hosts has led to the emergence of highly specialized biosynthetic capabilities, resulting in the production of structurally unique and biologically potent secondary metabolites. Many of these compounds exhibit striking bioactivities, including antimicrobial, anticancer, and immunosuppressive properties, making them highly valuable for drug discovery and commercial development.

In recent years, numerous novel bioactive compounds have been identified through the study of symbiotic systems, underscoring their immense potential as a source of previously untapped chemical diversity. (Nature Communications 14.1 (2023): 7650.) (Nature chemistry 14.6 (2022): 701-712.)This curated collection enables users to browse known host-microbe relationships and their associated compounds, serving as a valuable resource for natural product research.

❖ Elicitation: An invaluable strategy for unlocking natural product drug discovery

Elicitation has emerged as a pivotal strategy in natural product drug discovery, particularly for harnessing the rich biosynthetic potential of Actinobacteria. Although genome sequencing has revealed an abundance of biosynthetic gene clusters (BGCs) capable of producing diverse bioactive compounds, many remain silent or cryptic under standard laboratory conditions. This silence often stems from the absence of the complex ecological cues—such as nutrient limitation, microbial competition, or host-derived signals—that naturally trigger their expression in the environment. As traditional high-throughput screening methods have seen diminishing returns, elicitation offers a powerful means to revive interest in natural product discovery by reactivating these dormant pathways.(Nature Reviews Microbiology 18.10 (2020): 546-558.)

By mimicking natural environmental stimuli, elicitors—such as small signaling molecules, stress hormones—can effectively induce the expression of otherwise inaccessible BGCs. This approach not only expands the accessible chemical space for drug discovery but also increases the likelihood of identifying novel antibiotics and other therapeutic agents.To cater to this need, we manually collected elicitation-related metabolites from published literature, compiling compounds that have been experimentally shown to activate silent or poorly expressed biosynthetic gene clusters. This curated dataset serves as a valuable resource for understanding the chemical signals involved in natural product biosynthesis and supports the rational design of elicitation strategies in NP drug discovery.

❖ Co-culture microorganisms and engineered microorganisms for optimized production of high-value NPs

Recently years, deeper understanding in biosynthesis mechanisms, advances in synthetic biology and metabolic/genetic reprogramming strategies are evolving the NP research paradigm. In the nature, microorganisms merely grow and function (e.g., producing secondary metabolites) independently, but cooperate with other species in their surrounding living system. In addition, many synthetic gene clusters for biosynthesis of high-value NPs were usually silenced in natural organisms.

By manipulating the cultivation system or engineering metabolic pathways/synthetic gene clusters, NPs can be produced by organisms in more efficient and programmable manners. Co-culture and engineering natural species are two important synthetic biology strategies to achieve such purposes. By activating silenced synthetic pathways or introducing synthetic enzymes to model species, or by recovering microbe-microbe interactions, organism engineering and co-culture systems (also termed microbial consortia) are emerging strategies to produce novel NPs or increase yield of high-value NPs.

A comprehensive dataset of co-culture and engineered organisms is of importance for the NP research community, such as to deeper understand the potentials and diversity of biosynthesis space of organisms for NPs and drug discovery. To cater this need, we extensively searched PubMed and manually curated co-culture combinations and engineered organisms from literature.

❖ The workflow of developing NPASS is illustrated in the below figure