Micallef Melinda L, D'Agostino Paul M, Al-Sinawi Bakir, Neilan Brett A, Moffitt Michelle C
School of Science and Health, University of Western Sydney, Campbelltown, NSW 2560, Australia.
School of Science and Health, University of Western Sydney, Campbelltown, NSW 2560, Australia; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW 2052, Australia.
Mar Genomics. 2015 Jun;21:1-12. doi: 10.1016/j.margen.2014.11.009. Epub 2014 Dec 5.
Cyanobacteria produce a vast array of natural products, some of which are toxic to human health, while others possess potential pharmaceutical activities. Genome mining enables the identification and characterisation of natural product gene clusters; however, the current number of cyanobacterial genomes remains low compared to other phyla. There has been a recent effort to rectify this issue by increasing the number of sequenced cyanobacterial genomes. This has enabled the identification of biosynthetic gene clusters for structurally diverse metabolites, including non-ribosomal peptides, polyketides, ribosomal peptides, UV-absorbing compounds, alkaloids, terpenes and fatty acids. While some of the identified biosynthetic gene clusters correlate with known metabolites, genome mining also highlights the number and diversity of clusters for which the product is unknown (referred to as orphan gene clusters). A number of bioinformatic tools have recently been developed in order to predict the products of orphan gene clusters; however, in some cases the complexity of the cyanobacterial pathways makes the prediction problematic. This can be overcome by the use of mass spectrometry-guided natural product genome mining, or heterologous expression. Application of these techniques to cyanobacterial natural product gene clusters will be explored.
蓝细菌能产生大量天然产物，其中一些对人类健康有毒，而另一些则具有潜在的药用活性。基因组挖掘有助于识别和表征天然产物基因簇；然而，与其他门类相比，目前蓝细菌基因组的数量仍然较少。最近人们努力通过增加已测序蓝细菌基因组的数量来纠正这一问题。这使得能够识别出结构多样的代谢物的生物合成基因簇，包括非核糖体肽、聚酮化合物、核糖体肽、紫外线吸收化合物、生物碱、萜类化合物和脂肪酸。虽然一些已识别的生物合成基因簇与已知代谢物相关，但基因组挖掘也凸显了产物未知的基因簇（称为孤儿基因簇）的数量和多样性。最近开发了许多生物信息学工具来预测孤儿基因簇的产物；然而，在某些情况下，蓝细菌途径的复杂性使得预测存在问题。这可以通过使用质谱引导的天然产物基因组挖掘或异源表达来克服。将探讨这些技术在蓝细菌天然产物基因簇中的应用。
