NRPSs use amino acid monomers as substrates for synthesizing complex oligopeptides, whereas PKSs use acyl coenzyme A monomers to form elaborate chemical structures along a ketide backbone. Both NRPSs and PKSs are large (200- to 2,000-kDa), multifunctional enzymes that possess modular organization ( 4). In recent years, many microbiologists and biochemists have studied the distribution and functions of nonribosomal peptide synthetases (NRPSs) and modular polyketide synthases (PKSs), two similar molecular systems that are known to be involved in natural product synthesis in many bacteria, fungi, and plants ( 5, 16). Characterizing these compounds, as well as the molecular mechanisms underlying their synthesis, may provide important ecological insights, in addition to opportunities for the practical application of these compounds. The ecological significance of the cyanobacteria extends beyond their productivity, though, as many of these organisms are capable of modifying their habitats through the synthesis of biologically active natural products. The cyanobacteria are an ecologically, morphologically, and physiologically diverse group of organisms whose primary productivity contributes to the bioenergetic foundation for higher trophic levels in both marine and freshwater environments. These results underscore the potential variety of novel products being produced by these ubiquitous organisms. Phylogenetic analyses of the cyanobacterial NRPS and PKS fragments sequenced in this study, as well as those from the cyanobacterial genome projects, demonstrate that there is remarkable diversity and likely novelty of these genes within the cyanobacteria. In addition to validating the use of degenerate primers for the identification of PKS and NRPS genes in cyanobacteria, this study also defines numerous gene fragments that will be useful as probes for future studies of the synthesis of natural products in cyanobacteria. Our molecular data, when combined with genomic searches of finished and progressing cyanobacterial genomes, demonstrate that not all cyanobacteria contain NRPS and PKS genes and that the filamentous and heterocystous cyanobacteria are the richest sources of these genes and the most likely sources of novel natural products within the phylum. Using degenerate PCR and the sequencing of cloned products, we show that NRPSs and PKSs are common among the cyanobacteria tested. In this paper, we describe both the detection of natural product activities and the sequence identification of gene fragments from two molecular systems that have previously been implicated in natural product production, i.e., nonribosomal peptide synthetases (NRPSs) and modular polyketide synthases (PKSs), in diverse marine and freshwater cyanobacterial cultures. Natural products are a functionally diverse class of biochemically synthesized compounds, which include antibiotics, toxins, and siderophores.
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