[1S05m] 13. Microbial Engineering for Natural Products Synthesis - Part 1

10:45 AM - 11:00 AM JST(1:45 AM - 2:00 AM UTC)

[1MENP-02] Biosynthesis of sinefungins

○Richiro Ushimaru¹, Koki Ueno^1,2, Kazuki Shimada², Yi Yang², Ikuro Abe² (1. Kyushu Univ. (Japan), 2. Univ. Tokyo (Japan))

Keywords:

antifungal naural product,biosynthetic gene cluster,enzyme mechanism

Sinefungin is a nucleoside natural product produced by several Streptomyces species and is widely recognized as a potent inhibitor of S-adenosyl-L-methionine-dependent methyltransferases due to its close structural resemblance. The structure of sinefungin is characterized by the unusual C5′–C6′ carbon–carbon bond that links the ribose moiety of adenosine to an amino acid-derived side chain, posing a long-standing question regarding its biosynthetic origin. Early isotope-labeling studies suggested that adenine derivatives and arginine are precusors of sinefungin. In addition, cell-free assays indicated a possible involvement of a pyridoxal 5′-phosphate (PLP)-dependent enzyme. Despite these insights, the enzymatic basis and mechanism underlying the formation of the C–C bond between the nucleoside and amino acid moieties have remained elusive. Here, we report the genetic and biochemical elucidation of sinefungin biosynthesis, revealing the key enzymatic steps responsible for constructing its characteristic scaffold.