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bioRxiv · 10.1101/2020.12.30.424818

5-Deoxyadenosine Salvage by Promiscuous Enzyme Activity leads to Bioactive Deoxy-Sugar Synthesis in Synechococcus elongatus

Rapp, J.·Rath, P.·Kilian, J.·Brilisauer, K.·Grond, S.·Forchhammer, K.
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Abstract

7-Deoxysedoheptulose is an unusual deoxy-sugar, which acts as antimetabolite of the shikimate pathway thereby exhibiting antimicrobial and herbicidal activity. It is produced by the unicellular cyanobacterium Synechococcus elongatus PCC 7942, which has a small, stream-lined genome, assumed to be free from gene clusters for secondary metabolite synthesis. In this study, we identified the pathway for the synthesis of 7-deoxysedoheptulose. It originates from 5-deoxyadenosine, a toxic byproduct of radical S-adenosylmethionine (SAM) enzymes, present in all domains of life. Thereby we identified a novel 5-deoxyadenosine salvage pathway, which first leads to the synthesis and excretion of 5-deoxyribose and subsequently of 7-deoxysedoheptulose. Remarkably, all reaction steps are conducted by promiscuous enzymes. This is a unique example for the synthesis of a bioactive compound without involving a specific gene cluster. This challenges the view on bioactive molecule synthesis by extending the range of possible compounds beyond the options predicted from secondary metabolite gene clusters.

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Rapp, J., Rath, P., Kilian, J., Brilisauer, K., Grond, S., Forchhammer, K.. 2020-12-31. 5-Deoxyadenosine Salvage by Promiscuous Enzyme Activity leads to Bioactive Deoxy-Sugar Synthesis in Synechococcus elongatus. https://doi.org/10.1101/2020.12.30.424818

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