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Four novel proteasome inhibitors, TMC-95A-D (1-4) have been isolated from the fermentation broth of Apiospora montagnei Sacc. TC 1093, isolated from a soil sample. All of the molecular formulas of 1-4 were established as C(33)H(38)N(6)O(10) by high-resolution FAB-MS. Their planar structures were determined on the basis of extensive analyses of 1D and 2D NMR, and degradation studies. Compounds 1-4 have the same planar structures to each other, and are unique highly modified cyclic peptides containing L-tyrosine, L-aspargine, highly oxidized L-tryptophan, (Z)-1-propenylamine, and 3-methyl-2-oxopentanoic acid units. The absolute configuration at C-11 and C-36 of 1-4 was determined based on chiral TLC and HPLC analyses of their chemical degradation products. The ROESY analysis along with (1)H-(1)H coupling constants clarified the absolute stereochemistry at C-6, -7, -8, and -14 of the cyclic moieties. These studies revealed the relationships of 1-4 to be diastereomers at C-7 and C-36.

No abstract

The proBA operon, coding for y-glutamyl b a s e (GK) and y-glutamyl phosphate reductase (GPR), was cloned from the chromosome of the wild-type strain of Serratia marcescens Sr41. From our sequence data the proB (1101 bp) and proA (1472 bp) genes were shown to code for two proteins of M, 39169 and 44640, respectively. Analysis of expression of the ZacZstructural gene fused with theproBA promoter showed that theproBA operon is not subject to proline-mediated feedback repression. Amplification of the proBA operon enabled us to determine GK activity, which was inhibited in the presence of a low concentration of L-proline. Comparison of the amino acid sequences of the S. marcescens GK and GPR proteins with those of the GI( and GPR proteins from E. coZi revealed extensive similarities.

The polyether-macrolide antibiotic, boromycin, was isolated as a potent anti-human immunodeficiency virus (HIV) antibiotic from a fermentation broth of Streptomyces sp. A-3376. Boromycin was found to strongly inhibit the replication of the clinically isolated HIV-1 strain as well as the cultured strain in in vitro laboratory experiments. The mechanism for the anti-HIV activity of boromycin is suggested to involve blocking the later stage of HIV infection, and probably the maturity step for replication of the HIV molecule.