Department of Medicinal Chemistry and Pharmacognosy and Center for Biomolecular Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, 60607, USA.
J Ind Microbiol Biotechnol. 2019 Oct;46(9-10):1359-1364. doi: 10.1007/s10295-019-02187-1. Epub 2019 May 15.
Members of the diazaquinomycin class of natural products have shown potent and selective activity against Mycobacterium tuberculosis. However, poor aqueous solubility has prevented extensive studies in animal models thus far. Our long-term goal is to harness knowledge regarding diazaquinomycin biosynthesis towards the generation of derivatives for structure-activity relationship studies. We have previously sequenced the genomes of two diazaquinomycin-producing, actinomycete bacteria and identified putative daq biosynthetic gene clusters. Here, we report the heterologous expression of the daq gene cluster from the marine Streptomyces sp. F001 in S. coelicolor M1152. In addition to serving as functional proof for gene cluster assignment, the heterologous expression system reported here is expected to facilitate investigations aimed at elucidating diazaquinomycin biosynthesis.
氮杂喹诺霉素类天然产物对结核分枝杆菌具有很强的选择性活性。然而，较差的水溶性迄今为止阻碍了在动物模型中的广泛研究。我们的长期目标是利用氮杂喹诺霉素生物合成方面的知识来生成衍生物，以进行结构-活性关系研究。我们之前已经对两种产生氮杂喹诺霉素的放线菌进行了基因组测序，并鉴定了推定的 daq 生物合成基因簇。在这里，我们报告了海洋链霉菌 F001 的 daq 基因簇在 S. coelicolor M1152 中的异源表达。除了作为基因簇分配的功能证明外，这里报道的异源表达系统预计将有助于阐明氮杂喹诺霉素生物合成的研究。
