Sains Malaysiana 54(2)(2025): 461-471

http://doi.org/10.17576/jsm-2025-5402-12

The Global Regulator VeA Modulates ATP Sulfurylase to Mediate Adenosine Synthesis Resulting in Inhibitory Activity of Endophytic Fusarium solani against A549 Cells

(Pengawal Selia Global VeA Memodulasi ATP Sulfurilase untuk Mengantara Sintesis Adenosin Menghasilkan Aktiviti Perencatan Endofit Fusarium solani terhadap Sel A549)

YULING JIANG^1,2, LU CAI^1,2, QING XIAO², GUIHUA LIU², RONGFEI LIU^1,2, YAN ZHAO², ZHANGJIANG HE,^1,2,* & JICHUAN KANG^1,2

¹College of Pharmacy, Guizhou University, Guiyang, People’s Republic of China
² Engineering Research Center of the Utilization for Characteristic Bio-Pharmaceutical Resources in Southwest, Ministry of Education, Guizhou University, Guiyang 550025, China

Received: 29 April 2024/Accepted: 18 November 2024

Abstract

Adenosine is an endogenous nucleoside that promotes apoptosis in cancer cells. Overexpression of the global regulator VeA gene (FsveA) in Fusarium solani resulted in the accumulation of multiple secondary metabolites, including adenosine. In this study, we utilised transcriptome and metabolome data to speculate on the key genes that impact adenosine synthesis in fungi. The c35754.graph_c1 gene encodes an ATP sulfurylase (Fsmet3) that was significantly up-regulated in F. solani mutant overexpressing VeA (FsveA^OEV14). The qRT-PCR results were consistent with the transcriptome data, indicating that Fsmet3 was regulated by FsveA. Overexpression of Fsmet3 (Fsmet3^OE) resulted in a significant increase in adenosine content and the inhibitory activity of the fungi against the human non-small cell lung cancer A549 cells. Moreover, analysis of Fsmet3^OE metabolome showed that Fsmet3 not only up-regulated adenosine, but also significantly increased the accumulation of anti-tumor active substances such as resorufin and 13S-hydroxydodecanoic acid. Overall, our findings demonstrated that FsveA regulates Fsmet3 to mediate adenosine synthesis, resulting in potent inhibitory effects against A549 cells by endophytic F. solani.

Keywords: Adenosine; ATP sulfurylase; Fusarium solani; global regulator VeA; metabolomes

Abstrak

Adenosin adalah nukleosida endogen yang menggalakkan apoptosis dalam sel kanser. Pengekspresan melampau gen pengawal atur global VeA (FsveA) dalam Fusarium solani mengakibatkan pengumpulan pelbagai metabolit sekunder, termasuk adenosin. Dalam kajian ini, kami menggunakan data transkriptom dan metabolom untuk membuat spekulasi mengenai gen utama yang memberi kesan kepada sintesis adenosin dalam kulat. Gen c35754.graph_c1 mengekodkan ATP sulfurilase (Fsmet3) yang dikawal atur menaik dengan signifikan dalam F. solani mutan yang mengekspres VeA secara melampau (FsveA^OEV14). Hasil qRT-PCR didapati tekal dengan data transkriptom yang menunjukkan bahawa Fsmet3 dikawal atur oleh FsveA. Pengekspresan melampau Fsmet3 (Fsmet3^OE) mengakibatkan peningkatan signifikan dalam kandungan adenosin dan aktiviti perencatan kulat terhadap sel kanser paru-paru bukan sel kecil manusia A549. Selain itu, analisis metabolom Fsmet3^OE menunjukkan bahawa Fsmet3 bukan sahaja mengawal atur adenosin secara menaik, tetapi juga meningkatkan pengumpulan bahan aktif anti-tumor dengan signifikan seperti resorufin dan asid 13S-hidroksidodekanoik. Secara keseluruhan, penemuan kami menunjukkan bahawa FsveA mengawal atur Fsmet3 untuk memperantara sintesis adenosin, menghasilkan kesan perencatan yang kuat terhadap sel A549 oleh F. solani endofit.

Kata kunci: Adenosin; ATP sulfurilase; Fusarium solani; metabolom; pengawal atur global VeA

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*Corresponding author; email: zjhe3@gzu.edu.cn