On July 17, 2015, Diez, Veronica; Loznik, Mark; Taylor, Sandra; Winn, Michael; Rattray, Nicholas J. W.; Podmore, Helen; Micklefield, Jason; Goodacre, Royston; Medema, Marnix H.; Mueller, Ulrike; Bovenberg, Roel; Janssen, Dick B.; Takano, Eriko published an article.Application In Synthesis of H-Phg(4-OH)-OH The title of the article was Functional Exchangeability of Oxidase and Dehydrogenase Reactions in the Biosynthesis of Hydroxyphenylglycine, a Nonribosomal Peptide Building Block. And the article contained the following:
A key problem in the engineering of pathways for the production of pharmaceutical compounds is the limited diversity of biosynthetic enzymes, which restricts the attainability of suitable traits such as less harmful byproducts, enhanced expression features, or different cofactor requirements. A promising synthetic biol. approach is to redesign the biosynthetic pathway by replacing the native enzymes by heterologous proteins from unrelated pathways. In this study, we applied this method to effectively re-engineer the biosynthesis of hydroxyphenylglycine (HPG), a building block for the calcium-dependent antibiotic of Streptomyces coelicolor, a nonribosomal peptide. A key step in HPG biosynthesis is the conversion of 4-hydroxymandelate to 4-hydroxyphenylglyoxylate, catalyzed by hydroxymandelate oxidase (HmO), with concomitant generation of H2O2. The same reaction can also be catalyzed by O2-independent mandelate dehydrogenase (MdlB), which is a catabolic enzyme involved in bacterial mandelate utilization. In this work, we engineered alternative HPG biosynthetic pathways by replacing the native HmO in S. coelicolor by both heterologous oxidases and MdlB dehydrogenases from various sources and confirmed the restoration of calcium-dependent antibiotic biosynthesis by biol. and UHPLC-MS anal. The alternative enzymes were isolated and kinetically characterized, confirming their divergent substrate specificities and catalytic mechanisms. These results demonstrate that heterologous enzymes with different physiol. contexts can be used in a Streptomyces host to provide an expanded library of enzymic reactions for a synthetic biol. approach. This study thus broadens the options for the engineering of antibiotic production by using enzymes with different catalytic and structural features. The experimental process involved the reaction of H-Phg(4-OH)-OH(cas: 32462-30-9).Application In Synthesis of H-Phg(4-OH)-OH
The Article related to hydroxyphenylglycine biosynthesis oxidase dehydrogenase functional exchangeability, hmo, mdlb, uhplc-ms, calcium-dependent antibiotics, l-hpg biosynthesis, nonribosomal peptide, synthetic biology and other aspects.Application In Synthesis of H-Phg(4-OH)-OH
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