Structural insights into the biosynthesis of spirotetronate natural products

• Main Author: Byrne, Matthew James
• Published: University of Bristol 2015
• Subjects: 572
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.687814

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.