Abstract
The nucleotide sequence of the Penicillium chrysogenum Oli13 acvA gene encoding delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase, which performs the first step in penicillin biosynthesis, has been determined. The acvA gene contains an open reading frame of 11,238 bp encoding a protein of 3746 amino acids with a predicted mol. wt of 421,073 dalton. Three domains within the protein of approximately 570 amino acids have between 38% and 43% identity with each other and share similarity with two antibiotic peptide synthetases from Bacillus brevis as well as two other enzymes capable of performing ATP-pyrophosphate exchange reactions. The acvA gene is located close to the pcbC gene encoding isopenicillin N synthetase, the enzyme for the second step of beta-lactam biosynthesis, and is transcribed in the opposite orientation to it. The intergenic region of 1107 bp from which the acvA and pcbC genes are divergently transcribed has also been sequenced.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Banko G., Wolfe S., Demain A. L. Cell-free synthesis of delta-(L-alpha-aminoadipyl)-L-cysteine, the first intermediate of penicillin and cephalosporin biosynthesis. Biochem Biophys Res Commun. 1986 May 29;137(1):528–535. doi: 10.1016/0006-291x(86)91242-8. [DOI] [PubMed] [Google Scholar]
- Barredo J. L., Cantoral J. M., Alvarez E., Díez B., Martín J. F. Cloning, sequence analysis and transcriptional study of the isopenicillin N synthase of Penicillium chrysogenum AS-P-78. Mol Gen Genet. 1989 Mar;216(1):91–98. doi: 10.1007/BF00332235. [DOI] [PubMed] [Google Scholar]
- Barredo J. L., van Solingen P., Díez B., Alvarez E., Cantoral J. M., Kattevilder A., Smaal E. B., Groenen M. A., Veenstra A. E., Martín J. F. Cloning and characterization of the acyl-coenzyme A: 6-aminopenicillanic-acid-acyltransferase gene of Penicillium chrysogenum. Gene. 1989 Nov 30;83(2):291–300. doi: 10.1016/0378-1119(89)90115-7. [DOI] [PubMed] [Google Scholar]
- Bibb M. J., Findlay P. R., Johnson M. W. The relationship between base composition and codon usage in bacterial genes and its use for the simple and reliable identification of protein-coding sequences. Gene. 1984 Oct;30(1-3):157–166. doi: 10.1016/0378-1119(84)90116-1. [DOI] [PubMed] [Google Scholar]
- Carr L. G., Skatrud P. L., Scheetz M. E., 2nd, Queener S. W., Ingolia T. D. Cloning and expression of the isopenicillin N synthetase gene from Penicillium chrysogenum. Gene. 1986;48(2-3):257–266. doi: 10.1016/0378-1119(86)90084-3. [DOI] [PubMed] [Google Scholar]
- Charles I. G., Keyte J. W., Brammar W. J., Smith M., Hawkins A. R. The isolation and nucleotide sequence of the complex AROM locus of Aspergillus nidulans. Nucleic Acids Res. 1986 Mar 11;14(5):2201–2213. doi: 10.1093/nar/14.5.2201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fickett J. W. Recognition of protein coding regions in DNA sequences. Nucleic Acids Res. 1982 Sep 11;10(17):5303–5318. doi: 10.1093/nar/10.17.5303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gribskov M., Burgess R. R. Sigma factors from E. coli, B. subtilis, phage SP01, and phage T4 are homologous proteins. Nucleic Acids Res. 1986 Aug 26;14(16):6745–6763. doi: 10.1093/nar/14.16.6745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hawkins A. R. The complex Arom locus of Aspergillus nidulans. Evidence for multiple gene fusions and convergent evolution. Curr Genet. 1987;11(6-7):491–498. doi: 10.1007/BF00384611. [DOI] [PubMed] [Google Scholar]
- Ingolia T. D., Queener S. W. Beta-lactam biosynthetic genes. Med Res Rev. 1989 Apr-Jun;9(2):245–264. doi: 10.1002/med.2610090206. [DOI] [PubMed] [Google Scholar]
- Jensen S. E., Westlake D. W., Wolfe S. Deacetoxycephalosporin C synthetase and deacetoxycephalosporin C hydroxylase are two separate enzymes in Streptomyces clavuligerus. J Antibiot (Tokyo) 1985 Feb;38(2):263–265. doi: 10.7164/antibiotics.38.263. [DOI] [PubMed] [Google Scholar]
- Kleinkauf H., von Döhren H. Biosynthesis of peptide antibiotics. Annu Rev Microbiol. 1987;41:259–289. doi: 10.1146/annurev.mi.41.100187.001355. [DOI] [PubMed] [Google Scholar]
- Krätzschmar J., Krause M., Marahiel M. A. Gramicidin S biosynthesis operon containing the structural genes grsA and grsB has an open reading frame encoding a protein homologous to fatty acid thioesterases. J Bacteriol. 1989 Oct;171(10):5422–5429. doi: 10.1128/jb.171.10.5422-5429.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurahashi K. Biosynthesis of small peptides. Annu Rev Biochem. 1974;43(0):445–459. doi: 10.1146/annurev.bi.43.070174.002305. [DOI] [PubMed] [Google Scholar]
- Lara F., del Carmen Mateos R., Vázquez G., Sánchez S. Induction of penicillin biosynthesis by L-glutamate in penicillium chrysogenum. Biochem Biophys Res Commun. 1982 Mar 15;105(1):172–178. doi: 10.1016/s0006-291x(82)80027-2. [DOI] [PubMed] [Google Scholar]
- Lozoya E., Hoffmann H., Douglas C., Schulz W., Scheel D., Hahlbrock K. Primary structures and catalytic properties of isoenzymes encoded by the two 4-coumarate: CoA ligase genes in parsley. Eur J Biochem. 1988 Oct 1;176(3):661–667. doi: 10.1111/j.1432-1033.1988.tb14328.x. [DOI] [PubMed] [Google Scholar]
- MacCabe A. P., Riach M. B., Unkles S. E., Kinghorn J. R. The Aspergillus nidulans npeA locus consists of three contiguous genes required for penicillin biosynthesis. EMBO J. 1990 Jan;9(1):279–287. doi: 10.1002/j.1460-2075.1990.tb08106.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marahiel M. A., Krause M., Skarpeid H. J. Cloning of the tyrocidine synthetase 1 gene from Bacillus brevis and its expression in Escherichia coli. Mol Gen Genet. 1985;201(2):231–236. doi: 10.1007/BF00425664. [DOI] [PubMed] [Google Scholar]
- Nüesch J., Heim J., Treichler H. J. The biosynthesis of sulfur-containing beta-lactam antibiotics. Annu Rev Microbiol. 1987;41:51–75. doi: 10.1146/annurev.mi.41.100187.000411. [DOI] [PubMed] [Google Scholar]
- Ramón D., Carramolino L., Patiño C., Sánchez F., Peñalva M. A. Cloning and characterization of the isopenicillin N synthetase gene mediating the formation of the beta-lactam ring in Aspergillus nidulans. Gene. 1987;57(2-3):171–181. doi: 10.1016/0378-1119(87)90120-x. [DOI] [PubMed] [Google Scholar]
- Samson S. M., Belagaje R., Blankenship D. T., Chapman J. L., Perry D., Skatrud P. L., VanFrank R. M., Abraham E. P., Baldwin J. E., Queener S. W. Isolation, sequence determination and expression in Escherichia coli of the isopenicillin N synthetase gene from Cephalosporium acremonium. Nature. 1985 Nov 14;318(6042):191–194. doi: 10.1038/318191a0. [DOI] [PubMed] [Google Scholar]
- Smith D. J., Burnham M. K., Bull J. H., Hodgson J. E., Ward J. M., Browne P., Brown J., Barton B., Earl A. J., Turner G. Beta-lactam antibiotic biosynthetic genes have been conserved in clusters in prokaryotes and eukaryotes. EMBO J. 1990 Mar;9(3):741–747. doi: 10.1002/j.1460-2075.1990.tb08168.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith D. J., Burnham M. K., Edwards J., Earl A. J., Turner G. Cloning and heterologous expression of the penicillin biosynthetic gene cluster from penicillum chrysogenum. Biotechnology (N Y) 1990 Jan;8(1):39–41. doi: 10.1038/nbt0190-39. [DOI] [PubMed] [Google Scholar]
- Weckermann R., Fürbass R., Marahiel M. A. Complete nucleotide sequence of the tycA gene coding the tyrocidine synthetase 1 from Bacillus brevis. Nucleic Acids Res. 1988 Dec 23;16(24):11841–11841. doi: 10.1093/nar/16.24.11841. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weigel B. J., Burgett S. G., Chen V. J., Skatrud P. L., Frolik C. A., Queener S. W., Ingolia T. D. Cloning and expression in Escherichia coli of isopenicillin N synthetase genes from Streptomyces lipmanii and Aspergillus nidulans. J Bacteriol. 1988 Sep;170(9):3817–3826. doi: 10.1128/jb.170.9.3817-3826.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]
- de Wet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. doi: 10.1128/mcb.7.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Liempt H., von Döhren H., Kleinkauf H. delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase from Aspergillus nidulans. The first enzyme in penicillin biosynthesis is a multifunctional peptide synthetase. J Biol Chem. 1989 Mar 5;264(7):3680–3684. [PubMed] [Google Scholar]