majuscula [3]. More recently, compound isolation and structure elucidation from L. majuscula has been complemented with the characterization of biosynthetic gene clusters that encode a number of these compounds. The gene clusters for several potent anticancer and neurotoxic agents such as curacin A, barbamide, and the jamaicamides have provided new insight into the biosynthetic strategies and logic used by this organism for

compound production, as well as unique enzymes involved in unprecedented molecular tailoring reactions [4–7]. Despite considerable interest in pursuing cyanobacterial lead compounds as potential drug candidates, an adequate supply of these compounds for clinical research is often impossible to obtain without Sapanisertib clinical trial impractically large scale field collections or sophisticated and expensive synthetic methods [8, 9]. With some notable examples [10–13] it has been difficult to induce microbial gene clusters to produce their natural products in heterologous FGFR inhibitor hosts, and thus this technology is not Alvocidib manufacturer currently predictable [14]. Equally problematic, filamentous marine cyanobacteria such as Lyngbya grow slowly in laboratory culture, with doubling times in some cases of about 18 days [15]. One avenue for increasing compound production from marine cyanobacteria could be to take advantage of regulatory

elements associated with a biosynthetic gene cluster of interest. Although genetic

controls of several primary metabolic functions in cyanobacteria including circadian rhythms [16], heterocyst development [17], and nutrient uptake [18] have been described, information regarding transcriptional regulation of cyanobacterial secondary metabolites is currently limited to freshwater toxins such as the microcystins. The microcystins are potent hepatotoxins synthesized by several freshwater cyanobacteria of worldwide occurrence [19] and are generated via a mixed polyketide synthase/non-ribosomal peptide synthetase (PKS/NRPS) gene cluster [20]. Expression of the microcystin gene cluster is positively pheromone correlated with increased light intensity and red light in particular [21]. Moreover, the gene cluster has different transcription start sites depending on light levels [22]. Other environmental factors have been evaluated for their effects on microcystin production, and increasing evidence suggests that iron may be important. Transcription of genes from the microcystin gene cluster increases with iron starvation [23], and in the presence of iron, a ferric uptake regulator (Fur) protein appears to bind to the microcystin bidirectional promoter and may decrease microcystin production [24]. Because it complexes with iron and other metals [25] microcystin may therefore function as a siderophore.