ROLE OF VALINE AND ISOLEUCINE AS REGULATORS OF ACTINOMYCIN PEPTIDE FORMATION BY STREPTOMYCES CHRYSOMALLUS

Abstract

IKATZ, EDWARD (Rutgers, The State University, New Brunswick, N. J.), CLARENCE R. AWTALDRON, AND MARY Lou MEILONI. Role of valine and isoleucine as regulators of actinomycin peptide formation by Streptomyces chrysomallus.

A possible role of d-valine and related d-amino acids in repression of enzyme and actinomycin synthesis

“…On the other hand, D-valine may block a specific step in the formation of actinomycin biosynthetic proteins (e. g., activation of va-IyltRNA synthetase). This action appears unlikely in light of previous observations (Katz 1960;Katz et al 1961) that the D-amino acid does not inhibit growth of actinomycin-producing cultures. Conceivably, the D-amino acid may influence actinomycin production through carbon and/or nitrogen catabolite regulation (Martin and Demain 1980) --its slow uptake and metabolism ensuring a continuous supply of catabolite(s) that block specifically transcription of actinomycin biosynthetic genes over a long period of time.…”

“…cin D production by D-valine was an unexpected finding as we had considered it likely that the site of action of the D-amino acid involved the conversion of the L-amino acid to its D-form (Katz et al 1961;DiGirolamo et al 1964). The present data suggest alternative possibilities which may influence the biosynthetic process directly or indirectly.…”

“…D-Amino acids, often present as constituents of peptide antibiotics, can inhibit synthesis of the relevant antibiotic when provided in the culture medium. For example, D-valine inhibits synthesis of actinomycin (Katz 1960;Katz et al 1961;Yajima et al 1972) and penicillin (Demain 1956) and D-leucine blocks formation of etamycin (Kamal and Katz 1976) and polymyxin (DiGirolamo et al 1964). Moreover, radioisotope experiments have demonstrated that the L-form rather than its Disomer is the precursor of the D-amino acid in the antibiotic peptide (Arnstein and Margreiter 1958;Katz and Weissbach 1963;DiGirolamo et al 1964).…”

“…Moreover, radioisotope experiments have demonstrated that the L-form rather than its Disomer is the precursor of the D-amino acid in the antibiotic peptide (Arnstein and Margreiter 1958;Katz and Weissbach 1963;DiGirolamo et al 1964). The mechanism of D-amino acid inhibition * Present address: Department of Pediatrics, Section of Pediatric Hematology, University of Michigan, Ann Arbor, Michigan 48109-0864, USA Offprint requests to: E. Katz of antibiotic synthesis has not been elucidated; it has been suggested, however, that the exogenous D-amino acid may block the antibiotic synthetasecatalyzed reaction concerned with the racemization of the L-amino acid to its peptide-bound Dform (Katz et al 1961;DiGirolamo et al 1964). D-Glutamic acid and D-aspartic acid as well as a number of L-amino acids markedly repress the synthesis of kynurenine formamidase II, the second enzyme in the pathway from L-tryptophan to the actinomycin chromophore, by Streptomyces parvulus during short term experiments (Katz 1980).…”

Streptomyces nigra sp. nov. Is a Novel Actinobacterium Isolated From Mangrove Soil and Exerts a Potent Antitumor Activity in Vitro

“…Its antitumor activity was confirmed by Juliano and Stamp (1978) . Similarly, bleomycin, a natural hybrid peptide-polyketide metabolite and an antitumor drug, is produced by S. plicatus , S. chrysomallus , and S. verticillus ( Katz et al, 1961 ; Juliano and Stamp, 1978 ; Du et al, 2000 ; Lam et al, 2002 ; Cai et al, 2016 ; Lee J.H. et al, 2016 ).…”