The new antibiotic, XK-90, produced by Streptomyces sp. is active against Gram-positive and Gram-negative bacteria. The structure has been determined as N-acetyl-N'-(3-formyl-4-hydroxyphenyl)hydrazine (1) and is the second example of a naturally occurring antibiotic having the phenylhydrazine skeleton.

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A number of lysine-requiring auxotrophs of Ceplalosporium acremonium were investigated for incorporation of side-chain precursors and for accumulation of β-lactam compounds. One of the auxotrophs, Acremonium chrysogenum ATCC 20389, producing cephalosporin C and penicillin N only if grown in media supplemented with DL-α-amino-adipic acid (DL-α-AAA), was found to use L-S-carboxymethylcysteine (L-CMC) as a side-chain precursor for the synthesis of a new penicillin (RIT 2214). No corresponding cephalosporin was detected. The penicillin present in the culture filtrate, was concentrated by adsorption on activated carbon and successive column chromatography on Amberlite IRA-68 and Amberlite XAD-4. Final purification was achieved by cellulose column chromatography.
RIT 2214 was identified as 6-(D)-{[(2-amino-2-carboxy)-ethylthio]-acetamido}-penicillanic acid by spectral analysis, bioactivity spectrum, elucidation of side-chain structure and finally by semisynthesis. Its biological properties were also evaluated.

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The constituent fatty acid of cerexin A was elucidated to be β-hydroxy isoundecanoic acid by gas chromatography, mass spectrometry and nuclear magnetic resonance. The asparaginyl asparagine linkage in the amino acid sequence of the antibiotic, which has been previously described, was proved to be a normal α-carboxylpeptide bond by dehydration-reduction procedure. The three asparagine residues in the sequence were isolated separately and their
chiralities were determined. The structure of cerexin A was concluded from the above results.

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The structure of cerexin B was examined. The constituent fatty acids were elucidated by gas chromatography and mass spectrometry to be β-hydroxy isodecanoic acid, β-hydroxy decanoic acid, β-hydroxy isoundecanoic acid and β-hydroxy anteisoundecanoic acid. The configurations of constituent amino acids were determined as asparagine (2D, 1L), valine (D), phenylalanine (D), allo-threonine (D), tryptophan (D), andallo-isoleucine (D) from their optical activities. Treatment with conc. hydrochloric acid cleaved at the γ-hydroxylysine residue to give two peptide fragments, one of which (the N-terminal side) was then deacylated with Polymyxin Acylase. Their amino acid sequences were examined by EDMAN degradation. From the results and analogy to cerexin A, the structure of cerexin B was deduced.

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From the culture broth of Bacillus cereus 60-6, in which antibiotic production was improved, a new antibiotic, named cerexin C, was isolated. Similarly, a new antibiotic, cerexin D, was isolated from the culture broth of Bacillus cereus Gp-3. Cerexins C and D are closely related to cerexins A and B in their physico-chemical and antimicrobial properties. In fact cerexins C and D are peptides essentially identical with cerexins A and B except for the presence of a lysine residue in place of the γ-hydroxylysine residue.

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Sorbistin A₁ (1b) and sorbistin B (1a), bioactive components of a new type of aminoglycoside antibiotic produced by a strain of Pseudomonas species, have been converted into a key intermediate 3 by blocking of the 1- and 4-amino groups of sorbistins with dimedone and subsequent deacylation of the 4'-N-acyl group. Some 4'-N-acyl analogs of sorbistin (1e-1t) have been synthesized by 4'-N-acylation of 3 with an appropriate reactive derivative of carboxylic acids (mixed anhydride, acid chloride or activated ester) followed by deblocking of the protected group with bromine or sodium nitrite. Chemical interconversion of three natural sorbistins A₁ (1b), A₂ (1c) and B (1a) has been performed by this procedure. The 1-N-acyl (4a-4c) and the 1, 4'-N, N-diacyl analogs (6a-6c) have been prepared by direct N-acylation of sorbistin D (1d) (the 4'-desacyl derivative) and sorbistin A₁, respectively. On the other hand, the 4-N-acyl (5a and 5b) and the 4, 4'-N, N-diacyl derivatives (7a and 7b) have been prepared by acylation and subsequent hydrogenolysis of 1-N-Cbz-sorbistin D (4b) and 1-N-Cbz-sorbistin A, (6b), respectively.
Determination of in vitro antimicrobial activity showed that the 4'-N-propionyl (1b) and the 4'-N-cyclopropylcarbonyl (1s) derivatives are the most active members of the 4'-N-acyl derivatives. Elongation and shortening of the side chain and introduction of functional groups
decreased the activity. N-Acylation of the amino group at C-1 or at C-4 gave virtually inactive products.

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The M component of virginiamycin was found to be modified by whole cells or cell-free enzyme preparations of aStaphylococcus aureus strain. It was shown that this reaction proceeds by enzymatic acetylation of the secondary alcoholic function of the molecule, followed by a rapid chemical degradation of the O-acetylated product.

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Labeled acetate, propionate and p-aminobenzoic acid were efficiently incorporated into candicidin by phosphate-limited resting cells of Streptomyces griseus. The efficiency of incorporation in short-term experiments using phosphate-limited resting cells was similar to that achieved previously in long-term experiments using growing cells. (2-¹⁴C)Propionate was more efficiently incorporated than (1-¹⁴C)propionate, (U-¹⁴C)propionate, or (U-¹⁴C)-acetate. p-Aminobenzoic acid incorporation is linear over a 10-hour period while those of acetate or propionate reach a constant level after approximately 4 hours of incubation. Double-labeled candicidin of high specific activity was prepared by supplementing the resting cell system with (³H)acetate and (¹⁴C)p-aminobenzoic acid.

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The effect of paddy soils on mycobacillin and versicolin was investigated. Soil inactivated mycobacillin as determined by spectral analysis and microbiological assay. Soil can inactivate mycobacillin only at or above the threshold concentration (125-130 μg per 10 mg of soil), the excess being unreacted. No new peak appears in the ultraviolet spectrum (240-300 nm) while mycobacillin is inactivated. Soil is without any effect on versicolin.

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The relationship between the effect of different turimycin components on ribosomal peptidyltransferase of E. coli, antimicrobial activity and chemical structure were studied. Inhibition of peptidyltransferase as well as antimicrobial activity increased with the length of the aliphatic side chain in 4''-position of mycarose and decreased with acylation in 3-position of the lactone ring. Inhibition of peptidyltransferase is paralleled by inhibition of acceptor substrate binding.

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Moderate concentrations of bredinin (1.2×10^-5 M) strongly inhibited growth of L5178Y cells, with the effect being reversed by guanylic acid (GMP). However, at higher concentrations of bredinin the inhibition was not reversed completely by GMP added in excess. Bredinin was cytocidal at concentrations above 2×10^-5 M, but 5×10^-5 M bredinin in the presence of excess GMP, bredinin was cytostatic.
Bredinin inhibited nucleic acid synthesis of L5178Y cells, but bredinin itself was not incorporated into the nucleic acid. Inhibition of nucleic acid synthesis was clearly reversed by GMP. Similarly chromosomal aberrations in L5178Y cells caused by bredinin were reversed by GMP. In contrast, the effect of a high concentration of bredinin on cell multiplication was not reversed by GMP. The modal volume of L5178Y cells increased during incubation in the presence of bredinin and GMP for 24 hours, 5×10^-5 M bredinin with GMP causing a 70% increase in cell volume. This increase in cell volume was mainly due to an increase in the protein content of the cells.
The cytostatic effect of bredinin with GMP was reversed completely by adenosine-3', 5'-cyclic monophosphate (cyclic AMP). Other cyclic nucleotides and nucleotides were ineffective. The reversing effect of cyclic AMP on cell survival depended upon the concentration of GMP, and was not seen in the absence of GMP. It was concluded that cyclic AMP influences the secondary cytostatic effect of bredinin, and not the primary cytotoxic effect reversed by GMP.

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Spectinomycin inhibits the formation and causes dissociation of preformed specific cellfree initiation complexes prepared with the trinucleotide A-U-G or R₁₇ phage RNA, fmet-RNA_F and either 30S ribosomal subunits or 70S ribosomes. Both the initiation factor and the Mg²⁺-induced processes are subject to inhibition by spectinomycin. The only exception is the Mg²⁺-induced 70S initiation system formed with A-U-G which is stimulated by spectinomycin.

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The effects of acetyl kidamycin on RNA synthesis in HeLa cells were investigated. Acetyl kidamycin inhibited the synthesis of 45S pre-rRNA, heterogeneous nuclear RNA(HnRNA) and small molecular weight RNAs, though not to the same degree. The processing of 45S pre-rRNA into 18S and 28S rRNA and that of HnRNA into mRNA were not affected.

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