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During the course of our screening for squalene synthase inhibitors and Ras farnesylation inhibitors, a novel fungal culture was discovered to produce two structurally unique compounds, CP-225,917 and CP-263,114, as well as zaragozic acid A (squalestatin I). The two compounds are characterized by a bicyclo[4.3. 1]dec-l,6-diene core plus two extended alkyl chains. CP-225,917 and CP-263,114 inhibit Ras farnesyl transferase from rat brain with IC50 values of 6/zm and 20^m, respectively. CP-225,917 inhibits squalene synthase with an IC50 value of 43 /xm and CP-263,114 with an IC50 of 160/zm. The producing organism, though not fully classified, exhibits the characteristics of a sterile Phomaspecies.

Two new antibiotics, CJ-16,264 (I) and "CJ-16,367 (II), were isolated from the fermentation broth of an unidentified fungus CL39457. These antibiotics have a pyrrolizidinone skeleton, first discovered in fungi. Compounds I and II inhibit the growth of Gram-positive multi-drug resistant bacteria and some Gram-negative strains such as Moraxella catarrhalis and Escherichia coll with altered permeability (imp). Comparison of an antibacterial profile between the two compoundssuggested that the gamma-lactone portion of I is important for the activity.