GEOMAR Center for Marine Biotechnology (GEOMAR-Biotech), Research Unit Marine Natural Products Chemistry, GEOMAR Helmholtz Center for Ocean Research Kiel, Am Kiel-Kanal 44, 24106 Kiel, Germany.
Institute of Bioinformatics, International Technology Park, Bangalore, 560066 & Manipal Academy of Higher Education (MAHE), Manipal 576104, Karnataka, India.
Mar Drugs. 2020 Dec 30;19(1):14. doi: 10.3390/md19010014.
Red yeasts of the genus are of great interest to the biotechnological industry due to their ability to produce valuable natural products, such as lipids and carotenoids with potential applications as surfactants, food additives, and pharmaceuticals. Herein, we explored the biosynthetic potential of 50-3-19/20B collected from the Mid-Atlantic Ridge using modern genomics and untargeted metabolomics tools. 50-3-19/20B exhibited anticancer activity when grown on PDA medium, while antimicrobial activity was observed when cultured on WSP-30 medium. Applying the bioactive molecular networking approach, the anticancer activity was linked to glycolipids, namely polyol esters of fatty acid (PEFA) derivatives. We purified four PEFAs (-) and the known methyl-2-hydroxy-3-(1H-indol-2-yl)propanoate (). Their structures were deduced from NMR and HR-MS/MS spectra, but - showed no anticancer activity in their pure form. Illumina-based genome sequencing, assembly and standard biosynthetic gene cluster (BGC) analyses were used to illustrate key components of the PEFA biosynthetic pathway. The fatty acid producing BGC3 was identified to be capable of producing precursors of PEFAs. Some strains are able to convert inulin into high-yielding PEFA and cell lipid using a native exo-inulinase enzyme. The genomic locus for an exo-inulinase enzyme (g1629.t1), which plays an instrumental role in the PEFA production via the mannitol biosynthesis pathway was identified. This is the first untargeted metabolomics study on providing new genomic insights into PEFA biosynthesis.
红酵母属的酵母由于能够生产有价值的天然产物，如具有作为表面活性剂、食品添加剂和药物应用潜力的脂质和类胡萝卜素，而引起了生物技术行业的极大兴趣。在此，我们使用现代基因组学和非靶向代谢组学工具，研究了从中大西洋海脊采集的 50-3-19/20B 的生物合成潜力。50-3-19/20B 在 PDA 培养基上生长时表现出抗癌活性，而在 WSP-30 培养基上培养时则表现出抗菌活性。应用生物活性分子网络方法，将抗癌活性与糖脂联系起来，即脂肪酸的多元醇酯（PEFA）衍生物。我们分离得到了四种 PEFAs(-)和已知的甲基-2-羟基-3-(1H-吲哚-2-基)丙酸盐()。它们的结构是根据 NMR 和 HR-MS/MS 谱推导出来的，但在其纯形式下没有表现出抗癌活性。基于 Illumina 的基因组测序、组装和标准生物合成基因簇 (BGC) 分析用于说明 PEFA 生物合成途径的关键组成部分。鉴定出产生脂肪酸的 BGC3 能够产生 PEFA 的前体。一些菌株能够利用天然外切菊粉酶将菊粉转化为高产 PEFA 和细胞脂质。鉴定到参与 PEFA 生产的甘露糖醇生物合成途径的外切菊粉酶基因（g1629.t1）的基因组位置。这是针对 进行的首次非靶向代谢组学研究，为 PEFA 生物合成提供了新的基因组见解。
