As a combinatorial method of metabolic engineering and evolutionary engineering [1].reporter-guided mutant selection method (RGMS) was first reported as an efficient mutant selection method to improve lovastatin production in a filamentous fungus Aspergillus terreus [2].In that study a single resistance gene ble (resistant to phyleomycin) was used as the reporter,and 51% of the selected mutants were positive,i.e..lovastatin over-producing ones.