Cyanobacteria are a rich source of bioactive natural products that are valued as potential drug candidates and recognized as toxic hazards in the environment.  Genomic investigations have led to the characterization of several cyanobacterial toxin biosynthetic gene clusters, and these advances enable new approaches for metabolite expression and manipulation via genetic engineering.  Yet, the regulatory mechanisms responsible for expressing gene clusters in cyanobacteria remain poorly understood.  We are using the jamaicamide biosynthetic pathway from the filamentous marine cyanobacterium Lyngbya majuscula as a model to characterize DNA promoter regions and possible transcription factors necessary for secondary metabolite gene expression.  We focused our attention on searching for promoter regions upstream of the jamaicamide cluster and in the intergenic regions present between many of the ORFs.  RNA extraction and cDNA synthesis have revealed that all of these intergenic regions are transcribed except those upstream of the genes jamA and jamI.  Analysis of these upstream regions using a reporter gene assay has shown that both function as promoters, suggesting that the jamaicamide gene cluster could be regulated with transcription factors in at least two pathway locations.  We also developed a protein pulldown assay in attempting to isolate these transcription factors.  Pulldown experiments with lysate from L. majuscula using the region upstream of jamA as an oligonucleotide probe have led to the identification of two proteins that show homology to a transcription factor in another cyanobacterial genus.  The potential role of these proteins in the expression of jamaicamide is being evaluated and will be discussed.