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Production of Cephalosporin Intermediates by Feeding Adipic Acid to Recombinant Penicillium chrysogenum Strains Expressing Ring Expansion Activity

Bio/Technology volume 13, pages 58–62 (1995)Cite this article

We demonstrate a novel and efficient bioprocess for production of the cephalosporin intermediates, 7-aminocephalosporank acid (7-ACA) or 7-amino deacetoxycephalosporanic acid (7-ADCA). The Streptomyces clavuligerus expandase gene or the Cephalosporium acremonium expandase-hydroxylase gene, with and without the acetyltransferase gene, were expressed in a penicillin production strain of Penicillium chrysogenum. Growth of these transformants in media containing adipic acid as the side chain precursor resulted in efficient production of cephalosporins having an adipyl side chain, proving that adipyl-6-APA is a substrate for either enzyme in vivo. Strains expressing expandase produced adipyl-7-ADCA, whereas strains expressing expandase-hydroxylase produced both adipyl-7-ADCA and adipyl-7-ADAC (aminodeace-tylcephalosporanic acid). Strains expressing expandase-hydroxylase and acetyltransferase produced adipyl-7-ADCA, adipyl-7-ADAC and adipyl-7-ACA. The adipyl side chain of these cephalosporins was easily removed with a Pseudomonas-derived amidase to yield the cephalosporin intermediates.

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Author notes

  1. Christopher D. Reeves: Corresponding author.

Authors and Affiliations

  1. Panlabs, Inc., 11804 North Creek Parkway South, Bothell, WA, 98011

    Lorilee Crawford, Anthony M. Stepan, Phyllis C. McAda, John A. Rambosek & Christopher D. Reeves

  2. Merck & Company, Inc., P.O. Box 7, Elkton, VA, 22827

    Michael J. Confer & Victor A. Vinci

Authors
  1. Lorilee Crawford
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  2. Anthony M. Stepan
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  4. John A. Rambosek
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  5. Michael J. Confer
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  7. Christopher D. Reeves
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Crawford, L., Stepan, A., McAda, P. et al. Production of Cephalosporin Intermediates by Feeding Adipic Acid to Recombinant Penicillium chrysogenum Strains Expressing Ring Expansion Activity. Nat Biotechnol 13, 58–62 (1995). https://doi.org/10.1038/nbt0195-58

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