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PC-04

Molecular networking-guided OSMAC approach strategy uncovers anti-

lymphangiogeneic metabolites from endophytic Aspergillus niger ST17

1
2
,4
Hung-Yi Chen, Shih-Wei Wang, Tzong-Huei Lee, Andrea Gu, Ho-Cheng Wu,* Kuei-
3
3,4
Hung Lai* ,1,5,6

1 Ph.D. Program in Drug Discovery and Development Industry, Taipei Medical University,
Taipei, Taiwan
2 Institute of Biomedical Science, Mackay Medical College, New Taipei, Taiwan
3 Institute of Fisheries Science, National Taiwan University, Taipei, Taiwan
4 School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
5 Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan
6 Ph.D. Program in Clinical Drug Development of Herbal Medicine, Taipei Medical
University,
Taipei, Taiwan
* E-mail: hcwu@kmu.edu.tw; kueihunglai@tmu.edu.tw

Abstract
Cancer remains a leading cause of death in Taiwan and worldwide, with more than 60% of
patients succumbing to metastatic disease, underscoring the urgent need for effective anti-
metastatic therapeutics. Tumor lymphangiogenesis is a critical driver of tumor progression,
invasion, and metastasis, making its inhibition an attractive therapeutic strategy. In this study,
28 endophytes were isolated from the Taiwanese medicinal plant Scaevola taccada. Among
them, YPD-fermentates of Aspergillus niger ST17 exhibited potent inhibitory activity against
lymphatic endothelial cells (LECs) at 25 µg/mL. Application of the OSMAC approach (eight
solid and four liquid media) combined with LC-MS/MS molecular networking revealed that A.
niger ST17 produced the greatest chemical diversity when co-cultured with Discorea japonica
var. pseudoja. Large-scale fermentation and isolation yielded one new steroid compound and
ten known compounds. In LEC assays, compounds 3, 5, and 8 significantly reduced cell
survival at 30 µM (cell survival of 15±4%, 5±1%, and 0±3%). Molecular docking further
indicated favorable binding affinities of these isolates to anti-lymphangiogenic targets.
Collectively, these findings identify that A. niger ST17 co-cultured with D. japonica var.
pseudoja as a promising source of anti-lymphangiogenic metabolites with strong potential for
the development of anti-metastatic agents.

Keywords: Aspergillus niger; Secondary metabolites; OSMAC approach fermentation; Anti-
lymphangiogenesis; Molecular networking