Although many ferredoxins and ferredoxin reductases have been reported, many details about the homologous electron transfer system of P450s remain unclear. cyp166B1 gene is clustered with the putative ferredoxin (FDX6) in Streptomyces peucetius var. caesius ATCC 27952. Six ferredoxin reductases along with the putative ferredoxin were individually expressed in Escherichia coli and determined the probable primary pathway for dealkylation of 7-ethoxycoumarin as NADH -> FDR4 -> FDX6 -> CYP166B1. Further, mechanistic studies aimed at identifying the endogenous substrate of CYP166B1 would provide a more clear explanation on the homologous electron transfer system. (C) 2010 Elsevier Inc. All rights reserved.