Organization, evolution, and expression analysis of the biosynthetic gene cluster for scytonemin, a cyanobacterial UV-absorbing pigment.

Cyanobacteria are photosynthetic prokaryotes capable of protecting themselves from UV radiation through the biosynthesis of UV-absorbing secondary metabolites, such as the mycosporines and scytonemin. Scytonemin, a novel indolic-phenolic pigment, is found sequestered in the sheath, where it provides protection to the subtending cells during exposure to UV radiation. The biosynthesis of scytonemin is encoded by a previously identified gene cluster that is present in six cyanobacterial species whose genomes are available. A comparison of these clusters reveals that two major cluster architectures exist which appear to have evolved through rearrangements of large sections, such as those genes responsible for aromatic amino acid biosynthesis and through the insertion of genes that potentially confer additional biosynthetic capabilities. Differential transcriptional expression analysis demonstrated that the entire gene cluster is transcribed in higher abundance after exposure to UV radiation. This analysis helps delineate the cluster boundaries and indicates that regulation of this cluster is controlled by the presence or absence of UV radiation. The findings from an evolutionary phylogenetic analysis combined with the fact that the scytonemin gene cluster is distributed across several cyanobacterial lineages led to our proposal that the distribution of this gene cluster is best explained through an ancient evolutionary origin.

New tricks from ancient algae: natural products biosynthesis in marine cyanobacteria.

Cyanobacteria, among Earth's oldest organisms, have evolved sophisticated biosynthetic pathways to produce a rich arsenal of bioactive natural products. In consequence, cyanobacterial secondary metabolites have been an incredibly fruitful source of lead compounds in drug discovery efforts. Investigations into the biochemistry responsible for the creation of these compounds, complemented by genome sequencing efforts, are revealing unique enzymatic mechanisms not described or rarely described elsewhere in the natural world. Herein, we discuss recent advances in understanding the biosynthesis of three cyanobacterial classes of natural product: mixed polyketide synthase/non ribosomal peptide synthetase (PKS/NRPS) metabolites, aromatic amino acid-derived alkaloids, and ribosomally encoded cyclic peptides. The unique biosynthetic mechanisms employed by cyanobacteria are inspiring new developments in heterologous gene expression and biotechnology.

Cloning and biochemical characterization of the hectochlorin biosynthetic gene cluster from the marine cyanobacterium Lyngbya majuscula.

Cyanobacteria, or blue-green algae, are a rich source of novel bioactive secondary metabolites that have potential applications as antimicrobial or anticancer agents or useful probes in cell biology studies. A Jamaican collection of the cyanobacterium Lyngbya majuscula has yielded several unique compounds including hectochlorin ( 1) and the jamaicamides A-C ( 5- 7). Hectochlorin has remarkable antifungal and cytotoxic properties. In this study, we have isolated the hectochlorin biosynthetic gene cluster ( hct) from L. majuscula to obtain details regarding its biosynthesis at the molecular genetic level. The genetic architecture and domain organization appear to be colinear with respect to its biosynthesis and consists of eight open reading frames (ORFs) spanning 38 kb. An unusual feature of the cluster is the presence of ketoreductase (KR) domains in two peptide synthetase modules, which are predicted to be involved in the formation of the two 2,3-dihydroxyisovaleric acid (DHIV) units. This biosynthetic motif has only recently been described in cereulide, valinomycin, and cryptophycin biosynthesis, and hence, this is only the second such report of an embedded ketoreductase in a cyanobacterial secondary metabolite gene cluster. Also present at the downstream end of the cluster are two cytochrome P450 monooxygenases, which are likely involved in the formation of the DHIV units. A putative halogenase, at the beginning of the gene cluster, is predicted to form 5,5-dichlorohexanoic acid.