Advances in natural product discovery: strategies, technologies, and insights

doi:10.1007/s13659-025-00556-1

Natural Products and Bioprospecting ›› 2026, Vol. 16 ›› Issue (1): 3-3.DOI: 10.1007/s13659-025-00556-1

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Advances in natural product discovery: strategies, technologies, and insights

Buddha Bahadur Basnet^1,2, Zhen-Yi Zhou¹, Rajesh Basnet^4,5, Bin Wei¹, Hong Wang^1,3

1. College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China;
2. Central Department of Biotechnology, Tribhuvan University, Kathmandu, Nepal;
3. Key Laboratory of Marine Fishery Resources Exploitment, Utilization of Zhejiang Province, Zhejiang University of Technology, Hangzhou 310014, China;
4. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China;
5. University of Chinese Academy of Sciences International College, 19 Yuquan Road, Shijingshan District, Beijing 100049, China

Received:2025-08-10 Online:2026-03-25 Published:2026-02-14
Contact: Bin Wei,E-mail:binwei@zjut.edu.cn;Hong Wang,E-mail:hongw@zjut.edu.cn
Supported by:
The authors gratefully acknowledge the support from the National Key Research and Development Programs (nos. 2022YFC2804104 and 2022YFC2804700, China), the Fundamental Research Funds for the Provincial Universities of Zhejiang (no. RF-A2022013, China), the programs of the National Natural Science Foundation of China (no. 42276137, China), and Zhejiang International Sci‐Tech Cooperation Base for the Exploitation and Utilization of Nature Product.

Advances in natural product discovery: strategies, technologies, and insights

Buddha Bahadur Basnet^1,2, Zhen-Yi Zhou¹, Rajesh Basnet^4,5, Bin Wei¹, Hong Wang^1,3

1. College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China;
2. Central Department of Biotechnology, Tribhuvan University, Kathmandu, Nepal;
3. Key Laboratory of Marine Fishery Resources Exploitment, Utilization of Zhejiang Province, Zhejiang University of Technology, Hangzhou 310014, China;
4. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China;
5. University of Chinese Academy of Sciences International College, 19 Yuquan Road, Shijingshan District, Beijing 100049, China

通讯作者: Bin Wei,E-mail:binwei@zjut.edu.cn;Hong Wang,E-mail:hongw@zjut.edu.cn
基金资助:
The authors gratefully acknowledge the support from the National Key Research and Development Programs (nos. 2022YFC2804104 and 2022YFC2804700, China), the Fundamental Research Funds for the Provincial Universities of Zhejiang (no. RF-A2022013, China), the programs of the National Natural Science Foundation of China (no. 42276137, China), and Zhejiang International Sci‐Tech Cooperation Base for the Exploitation and Utilization of Nature Product.

Abstract

Abstract: Natural products (NPs) and their analogues have long underpinned therapies in humans, animals, and plants health, yet, discovering truly novel scaffolds remains a formidable challenge, even with the enormous diversity offered. Over the last two decades, breakthroughs in bioinformatics, cheminformatics, advanced analytical methods, synthetic biology toolkits, and optimized microbial culture have surmounted many of the bottlenecks that stalled NP research in the 1990s and 2000s. Researchers now deploy innovative extraction and purification protocols alongside high-throughput dereplication tools to fish trace metabolites out of complex matrices. These combined approaches not only enable the discovery and rigorous characterization of biosynthesized metabolites, bio-transformed analogues and new chemical entities but also allow precise tuning of biosynthetic gene clusters (BGCs) and culture conditions- modulation and optimization, dramatically improving yield, scalability, and cost-efficiency. Several of these newly unearthed compounds exhibit unique bioactivities that directly inspire drug-development programs against metabolic disorders, cancer drug resistance, and infectious diseases. In this review, we present an up-to-date, concise roadmap of natural product discovery (NPD), majorly covering strategies for awakening silent BGCs, genome mining, and late-stage diversification systems, and we discuss the current limitations and perspectives of rational NPD.

Key words: Natural products, Culturing modulation, Unexplored reservoirs, Genome mining, Natural product diversification

摘要： Natural products (NPs) and their analogues have long underpinned therapies in humans, animals, and plants health, yet, discovering truly novel scaffolds remains a formidable challenge, even with the enormous diversity offered. Over the last two decades, breakthroughs in bioinformatics, cheminformatics, advanced analytical methods, synthetic biology toolkits, and optimized microbial culture have surmounted many of the bottlenecks that stalled NP research in the 1990s and 2000s. Researchers now deploy innovative extraction and purification protocols alongside high-throughput dereplication tools to fish trace metabolites out of complex matrices. These combined approaches not only enable the discovery and rigorous characterization of biosynthesized metabolites, bio-transformed analogues and new chemical entities but also allow precise tuning of biosynthetic gene clusters (BGCs) and culture conditions- modulation and optimization, dramatically improving yield, scalability, and cost-efficiency. Several of these newly unearthed compounds exhibit unique bioactivities that directly inspire drug-development programs against metabolic disorders, cancer drug resistance, and infectious diseases. In this review, we present an up-to-date, concise roadmap of natural product discovery (NPD), majorly covering strategies for awakening silent BGCs, genome mining, and late-stage diversification systems, and we discuss the current limitations and perspectives of rational NPD.

关键词: Natural products, Culturing modulation, Unexplored reservoirs, Genome mining, Natural product diversification

Buddha Bahadur Basnet, Zhen-Yi Zhou, Rajesh Basnet, Bin Wei, Hong Wang. Advances in natural product discovery: strategies, technologies, and insights[J]. Natural Products and Bioprospecting, 2026, 16(1): 3-3.

Buddha Bahadur Basnet, Zhen-Yi Zhou, Rajesh Basnet, Bin Wei, Hong Wang. Advances in natural product discovery: strategies, technologies, and insights[J]. 应用天然产物, 2026, 16(1): 3-3.

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Advances in natural product discovery: strategies, technologies, and insights

Advances in natural product discovery: strategies, technologies, and insights

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