Structure function analysis of benzalacetone synthase from Rheum palmatum

Tsuyoshi Abe, Hiroyuki Morita, Hisashi Noma, Toshiyuki Kohno, Hiroshi Noguchi, Ikuro Abe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Benzalacetone synthase (BAS) is a plant-specific chalcone synthase (CHS) superfamily type III polyketide synthase (PKS) that catalyzes a one-step decarboxylative condensation of 4-coumaroyl-CoA with malonyl-CoA. The diketide forming activity of Rheum palmatum BAS is attributed to the characteristic substitution of the conserved active-site Phe215 with Leu (numbering in Medicago sativa CHS). To further understand the structure and function of R. palmatum BAS, four site-directed mutants (C197T, C197G, G256L, and S338V) were newly constructed. All the mutants did not change the product pattern, however, the activity was 2-fold increased in S338V, while reduced to half in G256L mutant. On the other hand, the C197 mutants were functionally almost identical to wild-type BAS, excluding the possibility that the second active-site Cys is involved in the enzyme reaction. Instead, homology modeling suggested a possibility that, unlike the case of CHS, BAS utilizes an alternative pocket to lock the coumaroyl moiety for the diketide formation reaction.

Original languageEnglish
Pages (from-to)3161-3166
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number11
DOIs
StatePublished - 2007/06/01

Keywords

  • Benzalacetone
  • Benzalacetone synthase
  • Chalcone synthase
  • Engineered biosynthesis
  • Type III polyketide synthase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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