Protostadienol biosynthesis and metabolism in the pathogenic fungus Aspergillus fumigatus.
Details of the fungal biosynthetic pathway to helvolic acid and other fusidane antibiotics remain obscure. During product characterization of oxidosqualene cyclases in Aspergillus fumigatus, we found the long-sought cyclase that makes (17Z)-protosta-17(20),24-dien-3beta-ol, the precursor of helvolic acid. We then identified a gene cluster encoding the pathway to helvolic acid, which is controlled by a transcription regulator (LaeA) associated with fungal virulence. Evidence regarding the evolutionary origin and taxonomic distribution of fusidane biosynthesis is also presented.
Lodeiro
Silvia
S
Department of Chemistry, Rice University, Houston, Texas 77005, USA.
Xiong
Quanbo
Q
Wilson
William K
WK
Ivanova
Yulia
Y
Smith
McKenzie L
ML
May
Gregory S
GS
Matsuda
Seiichi P T
SP
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005672:Fusidic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019751:Intramolecular Transferases / Q000235:genetics / Q000378:metabolism*; D015394:Molecular Structure; D013237:Stereoisomerism; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification*
D000900:Anti-Bacterial Agents; D014315:Triterpenes; C530466:protosta-13(17),24-dien-3beta-ol; D005672:Fusidic Acid; D019751:Intramolecular Transferases; C021924:lanosterol synthase; C011267:helvolic acid