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Title: Structural insights into the biosynthesis of spirotetronate natural products
Author: Byrne, Matthew James
ISNI:       0000 0004 5915 4709
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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Spirotetronates are a subclass of polyketide natural products that exhibit an array of potentially exploitable bioactivities. They are characterised by the presence of a tetronic acid ring spiro-linked to cyclohexene. A general route to their biosynthesis has been elucidated through numerous in vitro and in vivo studies. These studies have shown a conserved cassette of enzymes to be responsible for both the incorporation of the eponymous tetronic acid ring, and subsequent chemical modification of this ring. In addition to this, a highly unusual acetylation/deactylation event has been shown to be instrumental in priming spirotetronate intermediates for the [4+2] cyclo-addition that leads to the formation of the spiro-centre. Until recently it remained unclear as to whether or not [4+2] cyclo-addition in the biosynthesis of spirotetronates proceeded via an enzymaticallycatalysed transformation. Herein I will present the crystal structures of the first tetronic acid forming condensing enzyme abyA1, the first acetyl lyase abyA5 and the first reported naturally occurring Diels-Alderase abyU. This work provides a significant insight into the molecular basis of spirotetronate biosynthesis and lays a foundation upon which enzymes from spirotetronate pathways could be used in synthetic biology tbwards the production of non-natural tetronate containing polyketides.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available