Compounds that inactivate lipopolysaccharide (LPS) activity have the potential of being new antiinflammatory agents. Therefore, we searched among microbial secondary metabolites for compounds that inhibited LPS-stimulated adhesion between human umbilical vein endothelial cells (HUVEC) and HL-60 cells. By this screening, we found a cyclic lipopeptide surfactin from the culture broth of Bacillus sp. BML752-121F2 to be inhibitory. The addition of the surfactin prior to the LPS stimulation decreased HL-60 cell-HUVEC adhesion without showing any cytotoxicity. We confirmed that surfactin inhibited LPS-induced expression of ICAM-1 and VCAM-1 in HUVEC. It also inhibited the cellular adhesion induced by lipid A, the active component of LPS; but it did not inhibit TNF-a or IL-1b -induced cell adhesion. Then, surfactin was shown to suppress the interaction of lipid A with LPS-binding protein (LBP) that mediates the transport of LPS to its receptors. Finally, surface plasmon resonance (SPR) analysis revealed the surfactin to interact reversibly with lipid A. Thus, this Bacillus surfactin was shown to be an inhibitor of LPS-induced signal transduction, directly interacting with LPS.

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An acetylene-containing lipopeptide, jahanyne, was isolated from the marine cyanobacterium Lyngbya sp. Its gross structure was established by spectroscopic analyses, and the absolute configuration was clarified based on a combination of chiral HPLC analyses, spectroscopic analyses, and derivatization reactions. Jahanyne significantly inhibited the growth of human cancer cells and induced apoptosis in HeLa cells.