Bacha, N,Dao, HP,Atoui, A,Mathieu, F,O'Callaghan, J,Puel, O,Liboz, T,Dobson, ADW,Lebrihi, A;

2009

September

Fungal Genetics and Biology

Cloning and characterization of novel methylsalicylic acid synthase gene involved in the biosynthesis of isoasperlactone and asperlactone in Aspergillus westerdijkiae

Validated

()

Aspergillus westerdijkiae Polyketide synthase Asperlactone Isoasperlactone 6-Methylsalicylic acid POLYKETIDE SYNTHASES METABOLITES DERIVATIVES OCHRACEUS PROBES

46

742

749

Aspergillus westerdijkiae is the main producer of several biologically active polyketide metabolites including isoasperlactone and asperlactone. A 5298 by polyketide synthase gene "aomsas" has been cloned in Aspergillus westerdijkiae by using gene walking approach and RACE-PCR. The predicted amino acid sequence of aomsas shows an identity of 40-56% with different methylsalicylic acid synthase genes found in Byssochlamys nivea, P. patulum, A. terreus and Streptomyces viridochromogenes. Based on the reverse transcription PCR and kinetic secondary metabolites production studies, aomsas expression was found to be associated with the biosynthesis of isoasperlactone and asperlactone. Moreover an aomsas knockout mutant "ao Delta msas" of A. westerdijkiae, not only lost the capacity to produce isoasperlactone and asperlactone, but also 6-methylsalicylic acid. The genetically complemented mutant ao+msas restored the biosynthesis of all the missing metabolites. Chemical complementation through the addition of 6-methylsalicylic acid, aspyrone and diepoxide to growing culture of ao Delta msas mutant revealed that these compounds play intermediate roles in the biosynthesis of asperlactone and isoasperlactone. (C) 2009 Elsevier Inc. All rights reserved.

DOI 10.1016/j.fgb.2009.07.002