Tryptophan tyrocidine

There are several biologically important peptides which contain tyrosine but not tryptophan. These include small molecules with molecular weights of about 1000 or less. Molecules such as oxytocin, vasopressin, and tyrocidine A are cyclic, while others such as angiotensin II and enkephalin are linear. Schiller 19) has reviewed the literature up through 1984 on fluorescence of these and several other peptides. One major finding that has been reported recently is that the anisotropy and fluorescence intensity decays of many peptides are complex. This is especially evident in some of the tyrosine-containing peptides, and we expect that there will be considerable effort made over the next few years toward understanding the physical basis for these complex kinetics. 

Gramicidin contains no acidic or basic groups. Tyrocidine contains strongly basic groups due to ornithine residues. It can be isolated only as the hydrochloride. The crystalline mixture tyrocidine contains 1-omithine, 1-proUne, 1-valine, 1-leucine, d-phenylalanihe, 1-tryptophane, 1-tyrosine, 1-aspartic acid and 1-glutamic acid (11). 

Often, cells of a single microbial strain can synthesize more than one member of a chemical family. The final yields of the various members can be shifted by appropriate precursor pressure. The absence or presence of certain growth factors may accomplish this. In the absence of either exogenous phenylalanine or tryptophan, the ratio of tyrocidines A B C synthesized by Bacillus brevis is 1 3 7. If either L- or D-phenylalanine is provided, the main component formed is tyrocidine A. If L- or D-tryptophan is furnished, component D predominates when both phenylalanine and tryptophan are supplied, each of the four components is synthesized. I ... 

Mach, Reich and Tatum were able to demonstrate an inhibition of the biosynthesis of protein in cells of B. brevis by chloramphenicol and puromycin without affecting the synthesis of tyrocidine . Several analogues of amino acids were found, which inhibited the biosynthesis of tyrocidine without affecting that of protein and vice versa. In contrast to protein synthesis, the production of tyrocidine did not depend on the continuous synthesis of RNA. Furthermore, environmental factors were able to control the relative amounts of the different tyrocidines synthesized by genetically homogeneous cultures . Addition of phenylalanine to the culture medium resulted in the almost exclusive synthesis of tyrocidine A, whereas the unsupplemented culture produced tyrocidine A, B and C. In the presence of tryptophan, a new form of tyrocidine, called tyrocidine D, containing three tryptophan in place of three phenylalanine residues, was produced. This lack of absolute requirement for specific amino acids in the formation of a peptide bond is in contrast to the strict specificity of sequential incorporation of amino acids... 

Tyrocidine B, C H N O,]. Purification and amino acid sequence determination King, Craig, J. Am. Chem. Soc. 77, 6624, 6627 (1955). Synthesis Kuromizu, Izumiya, Experi-entia 26, 587 (1970). Possesses the same structure as tyrocidine A except that L-tryptophan replaces the l phenylalanine. Crystals from methanol + isopropyl ether. 

Dubos showed that tyrothricin could be separated into two components, gramicidin and tyrocidine. Craig showed that tyrocidine could be resolved into three components, tyrocidines A, B and C. Tyrocidine A has the structure XI and t5nrocidine B differs from XI only in containing an L-tryptophan residue in place of an L-phenylalanine residue . 

In an asparagine-glycerol-salts medium, the ratio of tyrocidine A B C is 1 3 7 if L-phenylalanine is added, the main component produced is tyrocidine A (Mach and Tatum, 1964). If L-tryptophane is added to the basal medium, component D is predominant when both L-phenylalanine and L-tryptophane are used, all four components are synthesized. Similar results are obtained with D-phenylalanine and D-tryptophane. 

Furthermore, by addition of appropriate amino acid analogs, it is possible to suppress formation of the peptide antibiotics with very httle alteration of protein synthesis. For example, D-phenylalanine inhibits production of bacitracin (Snoke and Cornell, 1964) threo-j8-phenylserine, j8-2-thienylserine, a-methyl-tryptophan, 5-methyltryptophane, and -fluorophenylalanine suppress tyrocidine synthesis (Mach et aL, I963) and a combination of norvaline, norleucine, and hydroxyproline depresses formation of gramicidin S (Winnick et al., I96I). 

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