Characterization of an Unusual α‐Oxoamine Synthase Off‐Loading Domain from a Cyanobacterial Type I Fatty Acid Synthase

Abstract

AbstractType I fatty acid synthases (FASs) are known from higher eukaryotes and fungi. We report the discovery of FasT, a rare type I FAS from the cyanobacterium Chlorogloea sp. CCALA695. FasT possesses an unusual off‐loading domain, which was heterologously expressed in E. coli and found to act as an α‐oxoamine synthase (AOS) in vitro. Similar to serine palmitoyltransferases from sphingolipid biosynthesis, the AOS off‐loading domain catalyzes a decarboxylative Claisen condensation between l‐serine and a fatty acyl thioester. While the AOS domain was strictly specific for l‐serine, thioesters with saturated fatty acyl chains of six carbon atoms and longer were tolerated, with the highest activity observed for stearoyl−coenzyme A (C18). Our findings suggest a novel route to α‐amino ketones via the direct condensation of iteratively produced long‐chain fatty acids with l‐serine by a FAS with a cis‐acting AOS off‐loading domain.