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

Type 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 alpha-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 (C-18). Our findings suggest a novel route to alpha-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.

Automated summary

We report the discovery of a rare type I fatty acid synthase (FasT) from the cyanobacterium Chlorogloea sp. CCALA695, which possesses an unusual off-loading domain that acts as an alpha-oxoamine synthase in vitro. This off-loading domain catalyzes the decarboxylative Claisen condensation between l-serine and a fatty acyl thioester, similar to serine palmitoyltransferases from sphingolipid biosynthesis. Our findings suggest a novel route to alpha-amino ketones by the direct condensation of long-chain fatty acids with l-serine.