NDLI: Directed evolution and rational approaches to improving Streptomyces clavuligerus deacetoxycephalosporin C synthase for cephalosporin production

Content Provider	Springer Nature Link
Author	Goo, Kian Sim Chua, Chun Song Sim, Tiow Suan
Copyright Year	2009
Abstract	It is approximately 60 years since the discovery of cephalosporin C in Cephalosporium acremonium. Streptomycetes have since been found to produce the structurally related cephamycin C. Studies on the biosynthetic pathways of these two compounds revealed a common pathway including a step governed by deacetoxycephalosporin C synthase which catalyses the ring-expansion of penicillin N to deacetoxycephalosporin C. Because of the therapeutic importance of cephalosporins, this enzyme has been extensively studied for its ability to produce these antibiotics. Although, on the basis of earlier studies, its substrate specificity was believed to be extremely narrow, relentless efforts in optimizing the in-vitro enzyme assay conditions showed that it is able to convert a wide range of penicillin substrates differing in their side chains. It is a member of 2-oxoglutarate-dependent dioxygenase protein family, which requires the iron(II) ion as a co-factor and 2-oxoglutarate and molecular oxygen as co-substrates. It has highly conserved HXDX n H and RXS motifs to bind the co-factor and co-substrate, respectively. With advances in technology, the genes encoding this enzyme from various sources have been cloned and heterologously expressed for comparative analyses and mutagenesis studies. A high level of recombinant protein expression has also enabled crystallization of this enzyme for structure determination. This review will summarize some of the earlier biochemical characterization and describe the mechanistic action of this enzyme revealed by recent structural studies. This review will also discuss some of the approaches used to identify the amino acid residues involved in binding the penicillin substrate and to modify its substrate preference for possible industrial application.
Starting Page	619
Ending Page	633
Page Count	15
File Format	PDF
ISSN	13675435
Journal	Journal of Industrial Microbiology and Biotechnology
Volume Number	36
Issue Number	5
e-ISSN	14765535
Language	English
Publisher	Springer-Verlag
Publisher Date	2009-03-07
Publisher Place	Berlin, Heidelberg
Access Restriction	Subscribed
Subject Keyword	Mutational approach Industrial application Cephalosporin synthesis Penicillin Enzyme improvement Microbiology Bioinformatics Biotechnology Genetic Engineering Inorganic Chemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Medicine Bioengineering Applied Microbiology and Biotechnology Biotechnology

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