A high-throughput screening of a microbial natural product library led to the discovery of two novel compounds named nivetetracyclates A and B (1 and 2), which were produced by Streptomyces niveus designated as LS2151. The backbone of the compounds contains a hydrotetracyclate not previously reported from a natural source. The structures of the compounds were elucidated by spectroscopic methods. The nivetetracyclates exhibited activity against human HeLa cells.