**1. Introduction**

Microbial natural products are an important source of drug lead. Mangrove streptomycetes were reported as a potential source of plenty of antiproliferative or anti-microbial chemicals with novel structures [1]. The bioinformatics of easily available genome information from microorganisms breaks the bottleneck of traditional natural product discovery to a certain extent, and secondary metabolites isolation guided by genome sequence has increasingly become a research frontier [2]. Genome mining and silent gene cluster activation unveil the potential of diverse secondary metabolites in bacteria [3–5]. The OSMAC (One Strain Many Compounds) approach has been proven to be a simple and powerful tool to mine new natural products [6,7]. Due to complexity profiles of secondary metabolites including intermediates, a strategy named "genetic dereplication" was also developed to simplify the profiles by eliminating the major known secondary metabolites' biosynthetic pathway, so that more easily detecting other novel compounds and/or reversing the precursor pools for other low expressed pathways in the microorganisms [8].

Previous studies reported that enterocin and its metabolites are the main and high-yield products in *Streptomyces qinglanensis* 172205 [9]. After the whole genome sequence was obtained, we analyzed the gene clusters of secondary metabolites, and found that more than 50% of them are coding for unknown compounds. However, enterocin was always detected in all of the media used during the OSMAC study. Hence, in this study, to mine the unknown compounds in strain 172205, we carried out the genetic dereplication strategy by which we deleted the enterocin biosynthetic gene cluster in genome and then detected the diversity of secondary metabolites profiles by OSMAC method. A mutant strain 172205Δ*enc* was generated by the whole enterocin biosynthetic gene cluster deletion using double-crossover homologous recombination and tested by HPLC fingerprint profiles for diverse products of crude extracts from 10 kinds of liquid fermentation media. The results showed that strain 172205Δ*enc* could produce the most diverse peaks on HPLC under fermentation in D.O. (dextrin-oatmeal) medium. Subsequently, a large-scale fermentation with D.O. medium was performed. After isolation and purification of the compounds from the crude extract, five new compounds including 15*R*-17,18-dehydroxantholipin (**1**), (3*E*,5*E*,7*E*)-3-methyldeca-3,5,7-triene-2,9-dione (**2**) and qinlactone A–C (**3**–**5**) were identified. Their structures were elucidated by one-dimensional (1D)/two-dimensional (2D) nuclear magnetic resonance spectroscopy (NMR) data, as well as electronic circular dichroism (ECD) calculation. In anti-microbial bioassay tests, compound **1** showed strong anti-*Staphylococcus aureus* and anti-*Candida albicans* activities with MIC (minimum inhibitory concentration) values of 0.78 μg/mL and 3.13 μg/mL, respectively. For antiproliferative bioactivity, compound **1** exhibited strong cytotoxicities against human breast cancer cell line MCF-7 and human cervical cancer cell line HeLa with IC50 values of 5.78 μM and 6.25 μM, respectively, while compound **2**–**4** showed weaker antiproliferative activities with IC50 values ranging from 129 to 207 μM. Therefore, the "genetic dereplication" strategy is useful to find compounds that synthesized by low expression gene clusters and would be of interest to colleagues in natural product discovery.
