Protostadienol synthase from Aspergillus fumigatus: Functional conversion into lanosterol synthase

Miki Kimura, Tetsuo Kushiro, Masaaki Shibuya, Yutaka Ebizuka, Ikuro Abe

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Oxidosqualene:protostadienol cyclase (OSPC) from the fungus Aspergillus fumigatus, catalyzes the cyclization of (3S)-2,3-oxidosqualene into protosta-17(20)Z,24-dien-3β-ol which is the precursor of the steroidal antibiotic helvolic acid. To shed light on the structure-function relationship between OSPC and oxidosqualene:lanosterol cyclase (OSLC), we constructed an OSPC mutant in which the C-terminal residues 702APPGGMR708 were replaced with 702NKSCAIS708, as in human OSLC. As a result, the mutant no longer produced the protostadienol, but instead efficiently produced a 1:1 mixture of lanosterol and parkeol. This is the first report of the functional conversion of OSPC into OSLC, which resulted in a 14-fold decrease in the Vmax/KM value, whereas the binding affinity for the substrate did not change significantly. Homology modeling suggested that stabilization of the C-20 protosteryl cation by the active-site Phe701 through cation-π interactions is important for the product outcome between protostadienol and lanosterol.

Original languageEnglish
Pages (from-to)899-902
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume391
Issue number1
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

  • Helvolic acid
  • Lanosterol synthase
  • Oxidosqualene cyclase
  • Protostadienol synthase
  • Steroidal antibiotics

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