The deacetoxycephalosporin C synthase (DAOCS) from Streptomyces clavuligerus was engineered with the aim of enhancing the conversion of penicillin G into phenylacetyl-7-aminodeacetoxycephalosporanic acid, a precursor of 7-aminodeacetoxycephalosporanic acid, for industrial application. A single round of random mutagenesis followed by the screening of 5,500 clones identified three mutants, G79E, ...

Terpenoids are a large structurally diverse group of natural products with an array of functions in their hosts. The large amount of genomic information from recent sequencing efforts provides opportunities and challenges for the functional assignment of terpene synthases that construct the carbon skeletons of these compounds. Inferring function from the sequence and/or structure of these enzym...

The deacetoxycephalosporin C synthase from Streptomyces clavuligerus was directly modified for enhancement of penicillin G expansion into phenylacetyl-7-aminodeacetoxycephalosporanic acid, an important intermediate in the industrial manufacture of cephalosporin antibiotics. Nine new mutants, mutants M73T, T91A, A106T, C155Y, Y184H, M188V, M188I, H244Q, and L277Q with 1.4- to 5.7-fold increases ...

Mackenzie, A., Studies on the Biosynthetic Pathways of Clavulanic Acid and Cephamycin C in Streptomyces clavuligerus. Doctoral dissertation. ISSN 1652-6880 ISBN 978-91-576-7318-3 The discovery of penicillin, a β-lactam antibiotic, changed the way humans thought about infectious disease. Unfortunately, the widespread use of antibiotics has lead to a concomitant increase in bacterial resistance t...

pounds is accomplished by means of a biosynthetic pathway which closely parallels the corresponding pathway to cephalosporin C in Cephalosporium acremonium. Two of the enzymes involved in this pathway, deacetoxycephalosporin C (DAOC) synthetase and DAOC hydroxylase, carry out sequential reactions in which penicillin N undergoes ring expansion to DAOC and then DAOC is hydroxylated at the C3 meth...

Clavulanic acid is a β-lactam compound with potent inhibitory activity against β-lactamases. Studies have shown that certain amino acids play essential roles in CA biosynthesis. However, quantitative evaluations of the effects of these amino acids are still needed in order to improve CA production. Here, we report a study of the nutritional requirements of Streptomyces clavuligerus for CA produ...