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

Abstract

Abstract7-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.

Hybrid Chemoenzymatic Synthesis of C7‐Sugars for Molecular Evidence of in vivo Shikimate Pathway Inhibition

“…The transketolase from S. elongatus was heterologously expressed and purified from E. coli as described by Brilisauer et al [2] . and we now optimized the reaction conditions [36] . Chemoenzymatic synthesis efficiently generated all the 7‐deoxy‐heptuloses 1 – 6 , confirming this approach of the hybrid synthesis as an efficient access to new heptuloses.…”