Rego Adriana, Sousa António G G, Santos João P, Pascoal Francisco, Canário João, Leão Pedro N, Magalhães Catarina
Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, 4450-208 Matosinhos, Portugal.
Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal.
Microorganisms. 2020 Feb 18;8(2):279. doi: 10.3390/microorganisms8020279.
Bacterial natural products (NPs) are still a major source of new drug leads. Polyketides (PKs) and non-ribosomal peptides (NRP) are two pharmaceutically important families of NPs and recent studies have revealed Antarctica to harbor endemic polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes, likely to be involved in the production of novel metabolites. Despite this, the diversity of secondary metabolites genes in Antarctica is still poorly explored. In this study, a computational bioprospection approach was employed to study the diversity and identity of PKS and NRPS genes to one of the most biodiverse areas in maritime Antarctica-Maxwell Bay. Amplicon sequencing of soil samples targeting ketosynthase (KS) and adenylation (AD) domains of PKS and NRPS genes, respectively, revealed abundant and unexplored chemical diversity in this peninsula. About 20% of AD domain sequences were only distantly related to characterized biosynthetic genes. Several PKS and NRPS genes were found to be closely associated to recently described metabolites including those from uncultured and candidate phyla. The combination of new approaches in computational biology and new culture-dependent and -independent strategies is thus critical for the recovery of the potential novel chemistry encoded in Antarctica microorganisms.
细菌天然产物(NPs)仍然是新药先导化合物的主要来源。聚酮化合物(PKs)和非核糖体肽(NRP)是两类具有重要药学意义的天然产物,最近的研究表明,南极洲存在特有的聚酮合酶(PKS)和非核糖体肽合成酶(NRPS)基因,可能参与新型代谢产物的合成。尽管如此,南极洲次生代谢产物基因的多样性仍未得到充分探索。在本研究中,采用了一种计算生物勘探方法,来研究PKS和NRPS基因在南极海洋生物多样性最高的地区之一——麦克斯韦湾的多样性和同一性。分别针对PKS和NRPS基因的酮合成酶(KS)和腺苷化(AD)结构域对土壤样本进行扩增子测序,结果显示该半岛存在丰富且未被探索的化学多样性。约20%的AD结构域序列与已鉴定的生物合成基因仅有远缘关系。发现几个PKS和NRPS基因与最近描述的代谢产物密切相关,包括来自未培养和候选门类的代谢产物。因此,计算生物学新方法与新的依赖培养和不依赖培养的策略相结合,对于挖掘南极微生物中潜在的新型化学物质至关重要。