Dong Hua, Ming Dengming
College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 South Puzhu Road, Jiangbei New District, Nanjing 211816, China.
Int J Mol Sci. 2023 Aug 4;24(15):12446. doi: 10.3390/ijms241512446.
In the world of microorganisms, the biosynthesis of natural products in secondary metabolism and the self-resistance of the host always occur together and complement each other. Identifying resistance genes from biosynthetic gene clusters (BGCs) helps us understand the self-defense mechanism and predict the biological activity of natural products synthesized by microorganisms. However, a comprehensive database of resistance genes is still lacking, which hinders natural product annotation studies in large-scale genome mining. In this study, we compiled a resistance gene database (RGDB) by scanning the four available databases: CARD, MIBiG, NCBIAMR, and UniProt. Every resistance gene in the database was annotated with resistance mechanisms and possibly involved chemical compounds, using manual annotation and transformation from the resource databases. The RGDB was applied to analyze resistance genes in 7432 BGCs in 1390 genomes from a marine microbiome project. Our calculation showed that the RGDB successfully identified resistance genes for more than half of the BGCs, suggesting that the database helps prioritize BGCs that produce biologically active natural products.
在微生物世界中，次生代谢中天然产物的生物合成与宿主的自我抗性总是相伴而生且相辅相成。从生物合成基因簇（BGCs）中鉴定抗性基因有助于我们理解自我防御机制，并预测微生物合成的天然产物的生物活性。然而，目前仍缺乏一个全面的抗性基因数据库，这阻碍了大规模基因组挖掘中的天然产物注释研究。在本研究中，我们通过扫描四个可用数据库：CARD、MIBiG、NCBIAMR和UniProt，编制了一个抗性基因数据库（RGDB）。利用手动注释和从资源数据库进行转换，数据库中的每个抗性基因都用抗性机制以及可能涉及的化合物进行了注释。将RGDB应用于分析来自一个海洋微生物群落项目的1390个基因组中7432个BGCs的抗性基因。我们的计算表明，RGDB成功鉴定出了超过一半BGCs的抗性基因，这表明该数据库有助于对产生具有生物活性天然产物的BGCs进行优先级排序。
