Through bioinformatic analysis,four putative regulatory genes,fiscRⅠ,fscRⅡ.fscRⅢand fscRⅣ,are identified in FR-008/candicidin biosynthetic gene cluster.In order to ascertain the involvement of regulatory genes on FR-008 biosynthesis,these four genes were disrupted respectively in ZYJ-6,a high-yield derivative of Streptomyces sp.FR-008.Mutants MXZ-1.MXZ-2.MXZ-3 and MXZ-4 were confirmed by PCR amplification,and further fermentation experiments demonstrated that the yield of FR-008/candicidin produced by these mutants were dramatically decreased in comparison with ZYJ-6.