Krause Janina, Handayani Ira, Blin Kai, Kulik Andreas, Mast Yvonne
Department of Microbiology/Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine, Faculty of Science, University of Tübingen, Tübingen, Germany.
Research Center for Biotechnology, Indonesian Institute of Sciences (LIPI), Cibinong, Indonesia.
Front Microbiol. 2020 Feb 18;11:225. doi: 10.3389/fmicb.2020.00225. eCollection 2020.
antibiotic regulatory protein (SARP) family regulators are well-known activators of antibiotic biosynthesis in streptomycetes. The respective genes occur in various types of antibiotic gene clusters encoding, e.g., for polyketides, ribosomally and non-ribosomally synthesized peptides, or β-lactam antibiotics. We found that overexpression of the SARP-type regulator gene from in leads to the activation of the silent undecylprodigiosin (Red) gene cluster. The activation happens upon the inducing function of PapR2, which takes over the regulatory role of RedD, the latter of which is the intrinsic SARP regulator of Red biosynthesis in . Due to the broad abundance of SARP genes in different antibiotic gene clusters of various actinomycetes and the uniform activating principle of the encoded regulators, we suggest that this type of regulator is especially well suited to be used as an initiator of antibiotic biosynthesis in actinomycetes. Here, we report on a SARP-guided strategy to activate antibiotic gene clusters. As a proof of principle, we present the PapR2-driven activation of the amicetin/plicacetin gene cluster in the novel Indonesian strain isolate sp. SHP22-7.
抗生素调控蛋白（SARP）家族调控因子是链霉菌中抗生素生物合成的著名激活因子。相应的基因存在于各种类型的抗生素基因簇中，这些基因簇编码例如聚酮化合物、核糖体合成和非核糖体合成的肽或β-内酰胺抗生素。我们发现，来自[具体来源未明确]的SARP型调控基因的过表达会导致沉默的十一烷基灵菌红素（Red）基因簇被激活。这种激活是在PapR2的诱导功能作用下发生的，PapR2取代了RedD的调控作用，RedD是[具体来源未明确]中Red生物合成的固有SARP调控因子。由于各种放线菌的不同抗生素基因簇中SARP基因广泛存在，且编码的调控因子具有统一的激活原理，我们认为这种类型的调控因子特别适合用作放线菌中抗生素生物合成的起始因子。在此，我们报道一种用于激活抗生素基因簇的SARP引导策略。作为原理验证，我们展示了PapR2驱动的新型印度尼西亚菌株分离物[具体菌株未明确]sp. SHP22 - 7中阿米菌素/普利西丁基因簇的激活。
