Summary
The effect of phenylacetic acid (PAA) and several analogs on the activity of isopenicillin N synthase (IPNS) and acyl-CoA: 6-APA acyltransferase (AT) fromPenicillium chrysogenum Wis 54-1255 has been tested. Whereas the substitution on the ring of a hydrogen atom by hydroxy-, methyl- or methoxy- groups did not cause any effect, the presence of halogens (Cl or Br) at positions 3 and/or 4 of PAA strongly inhibited these two enzymes. The replacement of hydrogen atoms by fluorine in certain positions also caused inhibition, but to a lesser extent.
Similar content being viewed by others
References
Alonso, M.J., F. Bermejo, A. Reglero, J.M. Fernández-Cañón, G. González de Buitrago and J.M. Luengo. 1988 Enzymatic synthesis of penicillins. J. Antibiotics 41: 1074–1084.
Baldwin, J.E. and M. Bradley 1990. Isopenicillin N synthase: mechanistic studies. Chem. Rev. 90: 1079–1088.
Baldwin, J.E., E.P. Abraham, G.L. Burge and H.H. Ting. 1985. Penicillin biosynthesis: direct biosynthetic formation of penicillin V and penicillin G. J. Chem. Soc. Chem. Commun. 1985: 1808–1809.
Baldwin, J.E., R.M. Adlington, M. James, C. Crabbe, C.G. Knight, T. Nomoto and C.J. Schofield. 1987. An effective substitute for α-aminoadipic acid in the enzymatic synthesis of penicillins. J. Chem. Soc. Chem. Commun. 1987: 806–807.
Brunner, R. and M. Rohr. 1975. Phenacyl: Coenzyme A ligase. In: Methods in Enzymology, Vol. XLIII (Hash, J.H., ed.), pp. 476–481. Academic Press, New York.
Fawcett, P. and E.P. Abraham. 1975. (l-α-Aminoadipyl)-l-cysteinyl-d-valine synthetase. In: Methods in Enzymology, Vol. XLIII (Hash, J.H., ed.), pp. 471–473, Academic Press, New York.
Fernández-Cañón, J.M., A. Reglero, H. Martínez-Blanco and J.M. Luengo. 1989. Uptake of phenylacetic acid byP. chrysogenum Wis 54-1255: a critical regulatory point in benzylpenicillin biosynthesis. J. Antibiotics 42: 1398–1409.
Konomi, T., S. Herchen, J. E. Baldwin, M. Yoshida, N.A. Hunt and A.L. Demain. 1979. Cell-free conversion of δ-(l-α-aminoadipyl)-l-cysteinyl-d-valine into an antibiotic with the properties of isopenicillin N inCephalosporium acremonium. Biochem. J. 184: 427–430.
López-Nieto, M.J., F.R. Ramos, J.M. Luengo and J.F. Martín. 1985. Characterization of the biosynthesis in vivo of α-aminoadipyl-cysteinyl-valine inPenicillium chrysogenum. Appl. Microbiol. Biotechnol. 22: 343–351.
Luengo, J.M., M.T. Alemany, F. Salto, F.R. Ramos, M.J. Lôpez-Nieto and J.F. Martín. 1986. Direct enzymatic synthesis of penicillin G using cyclases ofPenicillium chrysogenum andAcremonium chrysogenum. Bio/Technology 4: 44–47.
Luengo, J.M., J.L. Iriso and M.J. López-Nieto. 1986. Direct enzymatic synthesis of natural penicillins using phenylacetyl-CoA: 6-APA acyltransferase fromPenicillium chrysogenum: minimal and maximal side chain length requirements. J. Antibiotics 39: 1754–1759.
Martín-Villacorta, J., A. Reglero and J.M. Luengo. 1989. IV. Acyl-CoA: 6-APA acyltransferase ofPenicillium chrysogenum: studies on substrate specificity using phenylacetyl-CoA variants. J. Antibiotics 42: 1502–1505.
Penefsky, H.S.. 1977. Reversible binding of Pi by beef heart mitochondrial adenosine triphosphatase. J. Biol. Chem. 252: 2891–2899.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Martínez-Blanco, H., Reglero, A. & Luengo, J.M. Inhibition of penicillin biosynthetic enzymes by halogen derivatives of phenylacetic acid. Journal of Industrial Microbiology 13, 144–146 (1994). https://doi.org/10.1007/BF01583998
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01583998