4.6 Article

Functional characterization of key polyketide synthases by integrated metabolome and transcriptome analysis on curcuminoid biosynthesis in Curcuma wenyujin

期刊

SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
卷 7, 期 3, 页码 849-861

出版社

KEAI PUBLISHING LTD
DOI: 10.1016/j.synbio.2022.04.006

关键词

Metabolome; Curcuminoid; Transcriptome; Hydrogenated curcumin; Polyketide synthase

资金

  1. National Natural Science Foundation of China [82173919, 82104320]
  2. Natural Science Foundation of Zhejiang Province [LY21C050004, LQ22H280013]

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This study analyzed the metabolites of Curcuma wenyujin's leaf and tuber tissues, identifying 11 curcuminoid metabolites and revealing the biosynthesis pathway. Two candidate type III polyketide synthases (PKSs) were identified, with CwPKS1 being the first one capable of synthesizing hydrogenated derivatives of curcuminoids. Notably, a mutation (G219D) resulted in the complete inactivation of CwPKS1.
Leaf and tuber extracts of Curcuma wenyujin contain a mixture of curcuminoids. However, the curcuminoid constituents and their molecular mechanisms are poorly understood, and the relevant curcumin synthases remain unclear. In this study, we comprehensively compared the metabolite profiles of the leaf and tuber tissues of C. wenyujin. A total of 11 curcuminoid metabolites were identified and exhibited differentially changed contents in the leaf and tuber tissues. An integrated analysis of metabolomic and transcriptomic data revealed the proposed biosynthesis pathway of curcuminoid. Two candidate type III polyketide synthases (PKSs) were identified in the metabolically engineering yeasts, indicating that CwPKS1 and CwPKS2 maintained substrate and product specificities. Especially, CwPKS1 is the first type III PKS identified to synthesize hydrogenated derivatives of curcuminoid, dihydrocurcumin and tetrehydrocurcumin. Interestingly, the substitution of the glycine at position 219 with aspartic acid (G219D mutant) resulted in the complete inactivation of CwPKS1. Our results provide the first comparative metabolome analysis of C. wenyujin and functionally identified type III PKSs, giving valuable information for curcuminoids biosynthesis.

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