Abstract
Dynemicin is an enediyne natural product from Micromonospora chersina ATCC53710. Access to the biosynthetic gene cluster of dynemicin has enabled the in vitro study of gene products within the cluster to decipher their roles in assembling this unique molecule. This paper reports the crystal structure of DynF, the gene product of one of the genes within the biosynthetic gene cluster of dynemicin. DynF is revealed to be a dimeric eight-stranded β-barrel structure with palmitic acid bound within a cavity. The presence of palmitic acid suggests that DynF may be involved in binding the precursor polyene heptaene, which is central to the synthesis of the ten-membered ring of the enediyne core.
Highlights
Dynemicin A is an anthraquinone-fused ten-membered enediyne and a metabolite of Micromonospora chersina ATCC53710
The gene cluster contains a common iterative type I polyketide synthase (PKSE) that is essential for the biosynthesis of a precursor polyene which, in the presence of other accessory enzymes, forms the ten-membered enediyne core of dynemicin (Liu et al, 2003)
While some insight into the conversion of the iodoanthracene to the anthraquinone has recently been reported upon examination of the biosynthesis of sungeidines (Ma et al, 2021), which, like dynemicin, are anthraquinone-fused ten-membered enediynes, the steps leading to the iodoanthracene in addition to the enediyne core remain mostly unknown
Summary
Dynemicin A is an anthraquinone-fused ten-membered enediyne and a metabolite of Micromonospora chersina ATCC53710. Using homology to other characterized genomes, these genes have been annotated to suggest functions such as biosynthesis of the enediyne core, maturation and regulation, while there are those with as yet unknown functions (Gao & Thorson, 2008). The gene cluster contains a common iterative type I polyketide synthase (PKSE) that is essential for the biosynthesis of a precursor polyene (heptaene) which, in the presence of other accessory enzymes, forms the ten-membered enediyne core of dynemicin (Liu et al, 2003). While some insight into the conversion of the iodoanthracene to the anthraquinone has recently been reported upon examination of the biosynthesis of sungeidines (Ma et al, 2021), which, like dynemicin, are anthraquinone-fused ten-membered enediynes, the steps leading to the iodoanthracene in addition to the enediyne core remain mostly unknown. The DynF ortholog Sgd was very recently demonstrated by gene inactivation to be essential for sungeidine biosynthesis, and no intermediates, including the iodoanthracene, were detected (Ma et al, 2021),
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