Table 4_SSTDhunter: a curated gene database for investigating androgen producing potential in microbiota species.xlsx

Androgens are critical for the growth of prostate cells, as well as prostate tumor cells. For prostate cancer patients under Androgen Deprivation Therapy (ADT) such as castration treatment, investigating the potential for androgen production by gut microbes is crucial. In microbe species, the side chain cleavage activity of steroid-17, 20-desmolase (SSTD) is responsible for 11-oxy-androgens production by biotransformation from cortisol, as well as from other endogenous steroids and pharmaceutical glucocorticoids. The side-chain cleavage product of prednisone could significantly promote the proliferation of prostate cancer cells. The SSTD is a complex formed by N-terminal and C-terminal transketolases encoded by desA and desB genes, whose activity has been well-characterized in Clostridium scindens ATCC 35704. While a void still existed in evaluating the androgen producing potential by gut microbiota owing to relatively low abundance of SSTD-carrying species and the lack of professional gene database. Meanwhile, mining SSTD encoding genes in explosion sequencing data has become computationally expensive and time-consuming using comprehensive database. Here, a professional database consisted of SSTD-coding genes, named SSTDhunter, was constructed using a large-scale genomic analysis along with homologous genes as background. These SSTD-coding genes were reconstruction through comprehensive characteristics consisted of operon structures, sequence identities, phylogenetic topologies and comparative analysis. To reduce false positives, protein sequences of homologous genes tktA, which encode component of sugar transketolase, were also included in SSTDhunter database as background noise. SSTDhunter is for rapid investigation of SSTD-coding genes in massive metagenomic data, which is freely available at http://www.orgene.net/SSTDhunter/.

雄激素（Androgens）对于前列腺细胞及前列腺肿瘤细胞的生长至关重要。针对接受去势治疗等雄激素剥夺疗法（Androgen Deprivation Therapy, ADT）的前列腺癌患者而言，探究肠道微生物产生雄激素的潜力具有关键意义。在微生物物种中，类固醇17,20-脱溶酶（steroid-17, 20-desmolase, SSTD）的侧链裂解活性，负责通过将皮质醇、其他内源性类固醇以及药用糖皮质激素进行生物转化，进而生成11-氧雄激素（11-oxy-androgens）。泼尼松的侧链裂解产物可显著促进前列腺癌细胞的增殖。SSTD是由desA和desB基因编码的N端与C端转酮醇酶（transketolases）构成的复合体，其活性在斯氏梭菌（Clostridium scindens）ATCC 35704中已得到充分表征。然而，由于携带SSTD的物种丰度相对较低，且缺乏专业的基因数据库，评估肠道微生物群（gut microbiota）产生雄激素的潜力仍存在研究空白。同时，若使用综合数据库在海量测序数据中挖掘SSTD编码基因，将面临计算成本高昂、耗时耗力的问题。本研究通过大规模基因组分析，并以同源基因为背景，构建了一个包含SSTD编码基因的专业数据库，命名为SSTDhunter。这些SSTD编码基因通过综合特征进行重构，这些特征涵盖操纵子结构、序列同一性、系统发育拓扑结构以及比较分析结果。为降低假阳性率，编码糖转酮醇酶组分的同源基因tktA的蛋白质序列也被作为背景噪声纳入SSTDhunter数据库中。SSTDhunter可用于在海量宏基因组数据（metagenomic data）中快速筛查SSTD编码基因，该数据库可通过http://www.orgene.net/SSTDhunter/免费获取。