The Genome of Nothapodytes tomentosa and Characterization of Strictosidine Synthase Provide Insights into The Evolutionary Divergence of Camptothecin Biosynthesis

Yin Chen; Tian Tian; Zhiyin Yu; Can Wang; Xiaotao Tuo; Bingyan Xu; Chentao Wei; Jing Yang; Jian-Ping Huang; Yong-Jiang Wang; Sheng-Xiong Huang

doi:10.1016/j.eng.2025.10.030

Engineering ›› DOI: 10.1016/j.eng.2025.10.030

review-article

The Genome of Nothapodytes tomentosa and Characterization of Strictosidine Synthase Provide Insights into The Evolutionary Divergence of Camptothecin Biosynthesis

Yin Chen ^a^,^d^,¹
, Tian Tian ^a^,^d^,¹
, Zhiyin Yu ^b^,^c
, Can Wang ^b^,^c
, Xiaotao Tuo ^a
, Bingyan Xu ^a^,^d
, Chentao Wei ^a
, Jing Yang ^a^,^b^,^c
, Jian-Ping Huang ^a
, Yong-Jiang Wang ^a^,^b^,^c^,^*
, Sheng-Xiong Huang ^a^,^b^,^c^,^*

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Abstract

Camptothecin (CPT), a potent antitumor monoterpenoid indole alkaloid, is naturally produced by several plant species, including Nothapodytes tomentosa (N. tomentosa) and Camptotheca acuminata. However, the genomic basis and evolutionary history underlying CPT biosynthesis in N. tomentosa remain unclear. Here, we present a chromosome-level genome assembly of N. tomentosa and systematically annotate candidate genes implicated in CPT biosynthesis. Phylogenomic analysis revealed two recent whole-genome duplication events in N. tomentosa. Genomic analysis revealed a physically linked gene cluster comprising 9-hydroxy CPT O-methyltransferase 2 and loganic acid O-methyltransferase (LAMT) genes. Phylogenetic analyses of LAMT, 7-deoxyloganic acid hydroxylase, and secologanin synthase supported the evolutionary conservation of the iridoid pathway. However, functional characterization, active-site analysis, and phylogenetic reconstruction of strictosidine synthase suggested divergent evolutionary trajectories, indicating that N. tomentosa might employ an alternative enzymatic progress for strictosidine biosynthesis. This study provides foundational genomic insights into the evolution of CPT biosynthesis, offering valuable resources for metabolic engineering, pharmaceutical development, and the sustainable utilization and conservation of N. tomentosa as a medicinal plant.

Keywords

Nothapodytes tomentosa / Monoterpene indole alkaloids / Camptothecin / Biosynthesis / Evolutionary origin

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Yin Chen, Tian Tian, Zhiyin Yu, Can Wang, Xiaotao Tuo, Bingyan Xu, Chentao Wei, Jing Yang, Jian-Ping Huang, Yong-Jiang Wang, Sheng-Xiong Huang. The Genome of Nothapodytes tomentosa and Characterization of Strictosidine Synthase Provide Insights into The Evolutionary Divergence of Camptothecin Biosynthesis. Engineering DOI:10.1016/j.eng.2025.10.030

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