The Curious Case of CysE: Diversity and Distribution of Serine Acetyltransferases in Bacteria.

Serine acetyltransferase (CysE) is a member of the left-handed β-helix family of acetyltransferases that catalyze the rate limiting step in de novo cysteine biosynthesis. There are two isoforms of CysE that differ in length, with the shorter isoform lacking approximately 76 amino acids at the N-terminus of the protein from the serine acetyltransferase (SATase) domain. Here, we analyze the distribution and diversity of CysE isoforms across the bacterial kingdom. The isoforms can be classified into two discrete groups, with the truncated isoform prevalent in Gram-positive bacteria and the full-length isoform prevalent in Proteobacteria. Moreover, we demonstrate that the truncation is discrete with the loss of four N-terminal α-helices conserved for the truncated isoform. Using predictive modeling, we show that this truncation likely weakens the CysE trimer interface, potentially resulting in a trimeric assembly instead of the canonical CysE hexamer. This expands our understanding of CysE enzymes and their distribution across bacterial species, an important consideration given the increasing interest in targeting CysE enzymes for potential antimicrobials.