Natural product drug discovery has regained interest due to low production costs, structural diversity, and multiple uses of active compounds to treat various diseases. Attention has been directed towards medicinal plants as these plants have been traditionally used for generations to treat symptoms of numerous diseases. It is established that plants harbour microorganisms, collectively known as endophytes. Exploring the as-yet untapped natural products from the endophytes increases the chances of finding novel compounds. The concept of natural products targeting microbial pathogens has been applied to isolate novel antimycobacterial compounds, and the rapid development of drug-resistant Mycobacterium tuberculosis has significantly increased the need for new treatments against this pathogen. It remains important to continuously screen for novel compounds from natural sources, particularly from rarely encountered microorganisms, such as the endophytes. This review focuses on bioprospecting for polyketides and small peptides exhibiting antituberculosis activity, although current treatments against tuberculosis are described. It is established that natural products from these structure classes are often biosynthesised by microorganisms. Therefore it is hypothesised that some bioactive polyketides and peptides originally isolated from plants are in fact produced by their endophytes. This is of interest for further endophyte natural product investigations.
Dinoflagellates of the genus Alexandrium produce the neurotoxin saxitoxin (STX), responsible for paralytic shellfish poisoning (PSP) and accumulates in marine invertebrates. The recent identification of STX biosynthesis genes allowed us to investigate the expression of sxtA4 at different growth stages in Alexandrium catenella Group IV. We found no significant differences in expression of sxtA4, despite significant differences in STX levels at different growth stages (P < 0.023). Three reference genes were tested for normalisation: actin, cytochrome b (cob), and the large subunit ribosomal RNA (LSU rDNA). cob was most stably expressed but the combination of two reference genes, actin and cob, resulted in the best stability factor. Most genomic sequences of sxtA4 from A. catenella were in a clade that included sequences from Alexandrium fundyense Group I, however, one paralogue was not related to the others, suggesting recombination or lateral transfer. A comparison of the sxtA4 cDNA sequences with genomic DNA sequences indicated the possibility of transcript editing and the preferential transcription of certain genomic DNA loci. The results show that, in dinoflagellates, post-transcriptional mechanisms play a major role in the regulation of saxitoxin biosynthesis.
This is the first report on the fungal endophytic diversity of R. spathacea, and the isolation of an antimycobacterial compound from the plant which has been traditionally used for the treatment of tuberculosis symptoms.
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