Deciphering the Origin and Formation of Aminopyrrole Moiety in Kosinostatin Biosynthesis

Main observation and conclusion Kosinostatin (KST) contains an uncommon aminopyrrole moiety, whose biosynthesis has remained elusive. Herein, aminopyrrolinic acid, which was generated by an L-ectoine synthase-like enzyme KstB3 via cyclization of L-glutamine, was identified to be the real substrate of adenylation enzyme KstB1. Subsequently, a FAD-dependent dehydrogenase KstB4 along with a transglutaminase-like enzyme KstB6 were also involved in formation of aminopyrrole. These results provided an unusual pathway for 2-aminopyrrole formation in KST biosynthesis.