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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Phenoxazinone synthase: what's in a name?
Marilize Le Roes-Hill1, Candice Goodwin, Stephanie Burton
1Biocatalysis and Technical Biology Group, Department of Chemical Engineering, University of Cape Town, Private Bag 1, Rondebosch, 7701, Cape Town, South Africa.
Phenoxazinone synthases (PHS) are re-evaluated, revealing their connection to copper proteins and diverse roles in bacteria. This challenges traditional classification and suggests potential in novel antibiotic development.
Area of Science:
- Biochemistry and Molecular Biology
- Enzymology
- Microbial Genetics
Background:
- Phenoxazinone synthase (PHS) traditionally catalyzes oxidative coupling of o-aminophenols to form phenoxazinones.
- Recent sequence data suggests PHS relates to distinct copper protein groups, challenging its established classification.
- PHS enzymes have varied roles, including spore pigmentation (phsA) and antibiotic biosynthesis (GriF).
Purpose of the Study:
- To review the classification, distribution, and functions of phenoxazinone synthases (PHS).
- To compare PHS enzymes with copper oxidases at genetic and structural levels.
- To explore potential applications of PHS in developing new antibiotics.
Main Methods:
- Review of existing literature on phenoxazinone synthases (PHS).
- Analysis of sequence-based information to determine PHS relationships.
- Comparative study of PHS and copper oxidases at genetic and structural levels.
Main Results:
- Traditional PHS classification conflicts with sequence data linking them to copper protein families.
- PHS enzymes exhibit diverse roles, exemplified by spore pigmentation in Streptomyces antibioticus and grixazone biosynthesis in Streptomyces griseus.
- These distinct roles suggest convergent evolution among PHS enzymes.
Conclusions:
- Phenoxazinone synthases (PHS) represent a group with diverse evolutionary origins and functions, linked to copper proteins.
- The study highlights convergent evolution in PHS roles, such as in Streptomyces species.
- PHS enzymes offer potential for biotechnological applications, particularly in the synthesis of novel antibiotics.
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