Rodríguez-Peña Karol, Gómez-Román Maria Paula, Macías-Rubalcava Martha Lydia, Rocha-Zavaleta Leticia, Rodríguez-Sanoja Romina, Sánchez Sergio
Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Tercer Circuito Exterior s/n, 04510, Ciudad de México, México.
Departamento de Biotecnología. Boulevard Cuauhnáhuac #566, Universidad Politécnica del Estado de Morelos, Col. Lomas del Texcal, Jiutepec, Morelos, CP, 62550, México.
Appl Microbiol Biotechnol. 2022 Apr;106(8):3173-3190. doi: 10.1007/s00253-022-11915-0. Epub 2022 Apr 11.
The Embleya genus is a new member of the Streptomycetaceae family formed by only two species isolated from soil (Embleya scabrispora and Embleya hyalina). Strain NF3 is an endophytic actinobacterium obtained from the medicinal tree Amphipterygium adstringens. By 16S rRNA gene analysis, NF3 strain was identified as Embleya sp., closely related to E. hyalina. In our interest to deep into the NF3 strain features, a bioinformatic study was performed on the Embleya genus based on their genome information to produce secondary metabolites. A comparative analysis of the biosynthetic gene clusters (BGCs) of NF3 with the two released Embleya genomes revealed that NF3 has 49 BGCs, E. scabrispora DSM41855 has 50 BGCs, and E. hyalina NBRC13850 has 46 BGCs. Although bearing similar cluster numbers, the three strains shared only 25% of the BGCs information. NF3 encoded the nybomycin cluster detected in E. hyalina NBRC13850 and lacked the hitachimycin cluster present in E. scabrispora DSM41855. On the contrary, strain NF3 contained a cluster for the anthracycline steffimycin, neither encoded by E. hyalina NBRC13850 nor by E. scabrispora DSM41855. Our results and previous characterization studies supported strain NF3 as a new member of the genus Embleya. The chemical analysis of the steffimycins produced by strain NF3 showed the production of eight compounds of the steffimycins and steffimycinone families. Four of these molecules have already been described: steffimycin B, steffimycin C, 8-demethoxy-10-deoxysteffimycinone, and 7-deoxiesteffimycinone, and four are new natural products: 8-demethoxysteffimycin B, 8-demethoxy-10-deoxysteffimycin B, 7-deoxy-8-demethoxysteffimycinone, and 7-deoxy-10-deoxysteffimycinone. With this information, we proposed an alternative pathway to produce StefB. Among steffimycins, StefB was the main compound produced by this strain (29.8%) and showed the best cytotoxic activity. KEY POINTS: • The Embleya genus and its biosynthetic potential • An alternative biosynthetic pathway for steffimycins biosynthesis • Four new natural products of the steffimycin family.
恩布利亚属是链霉菌科的一个新成员，该属仅由从土壤中分离出的两个物种组成（粗糙孢恩布利亚菌和透明恩布利亚菌）。菌株NF3是从药用树收敛双翅果中获得的一种内生放线菌。通过16S rRNA基因分析，NF3菌株被鉴定为恩布利亚菌属，与透明恩布利亚菌密切相关。为深入了解NF3菌株的特性，基于恩布利亚属的基因组信息对其进行了生物信息学研究，以生产次级代谢产物。将NF3的生物合成基因簇（BGC）与已公布的两个恩布利亚基因组进行比较分析，结果显示NF3有49个BGC，粗糙孢恩布利亚菌DSM41855有50个BGC，透明恩布利亚菌NBRC13850有46个BGC。尽管这三个菌株的基因簇数量相似，但它们共享的BGC信息仅为25%。NF3编码了在透明恩布利亚菌NBRC13850中检测到的nybomycin基因簇，并且缺少粗糙孢恩布利亚菌DSM41855中存在的hitachimycin基因簇。相反，NF3菌株含有一个用于蒽环类化合物司替夫霉素的基因簇，该基因簇在透明恩布利亚菌NBRC13850和粗糙孢恩布利亚菌DSM41855中均未编码。我们的结果和先前的特性研究支持NF3菌株是恩布利亚属的一个新成员。对NF3菌株产生的司替夫霉素进行化学分析，结果显示产生了司替夫霉素和司替夫米酮家族的8种化合物。其中4种分子已被描述：司替夫霉素B、司替夫霉素C、8-去甲氧基-10-脱氧司替夫米酮和7-脱氧司替夫米酮，另外4种是新的天然产物：8-去甲氧基司替夫霉素B、8-去甲氧基-10-脱氧司替夫霉素B、7-脱氧-8-去甲氧基司替夫米酮和7-脱氧-10-脱氧司替夫米酮。基于这些信息，我们提出了一种生产司替夫霉素B的替代途径。在司替夫霉素中，司替夫霉素B是该菌株产生的主要化合物（29.8%），并且表现出最佳的细胞毒性活性。
• 恩布利亚属及其生物合成潜力
• 司替夫霉素生物合成的替代生物合成途径
• 司替夫霉素家族的4种新天然产物
