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College of Life Sciences: Jianquan Liu’s Team Has Revealed the Evolutionary Origin of Camptothecin Biosynthesis

Date:Jun 17, 2021

On June 10, 2021, Jianquan Liu’s research team published in Nature Communications their research results in an online paper entitled “A Chromosome-level Camptotheca Acuminata Genome Assembly Provides Insights into the Evolutionary Origin of Camptothecin Biosynthesis.”

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The team has assembled and annotated the Camptotheca genome at high quality chromosome level through PacBio and HiC technology, which was superior to the previously published version of the second generation genome based on the Illumina platform in accuracy, continuity and gene annotation.

“On the basis of annotated metabolites and enzymes identified11, the camptothecin biosynthetic pathway in C.acuminata is similar to that of some other MIAs, such as vinblastine and vincristine in Catharanthus roseus (L.) G.Don. Both pathways synthesize complex intermediate organic molecules (e.g., geraniol, 8-oxogeranial12,13,14, iridodial15, 7-deoxyloganetic acid16, 7-deoxyloganic acid, and loganic acid17) using the same set of enzymes, which are presumably encoded by homologous genes.” (Introduction)

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Comparison of camptothecin and vinblastine/vincristine biosynthesis pathways

“Camptothecin and its derivatives are widely used for treating malignant tumors. Previous studies revealed only a limited number of candidate genes for camptothecin biosynthesis in Camptotheca acuminata, and it is still poorly understood how its biosynthesis of camptothecin has evolved. Here, we report a high-quality, chromosome-level C.acuminata genome assembly. We find that C.acuminata experiences an independent whole-genome duplication and numerous genes derive from it are related to camptothecin biosynthesis. Comparing with Catharanthus roseus , the loganic acid O-methyltransferase (LAMT) in C. acuminata fails to convert loganic acid into loganin. Instead, two secologanic acid synthases (SLASs) convert loganic acid to secologanic acid. The functional divergence of the LAMT gene and positive evolution of two SLAS genes, therefore, both contribute greatly to the camptothecin biosynthesis in C. acuminata. Our results emphasize the importance of high-quality genome assembly in identifying genetic changes in the evolutionary origin of a secondary metabolite.” (Abstract)

Dr. Minghui Kang of the College of Life Sciences is the first author, and Professor Jianquan Liu is the corresponding author. This work was supported equally by the Strategic Priority Research Program of Chinese Academy of Sciences, National Key Research and Development Program of China, and the National Natural Science Foundation of China.

https://www.nature.com/articles/s41467-021-23872-9

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