operon of Streptococcus pneumoniae regulates metal homeostasis and 1 cellular metabolism during zinc-stress 2 3 11 12 13 14 Running Head: S. pneumoniae metabolism altered by zinc-sensitive operon 15 16 17 Corresponding author: Justin A. Thornton, thornton@biology.msstate.edu 18 19 20 21induced during zinc-limiting conditions. This operon was found to be regulated by a zinc-47 dependent regulator (SP1433) that functions independently of the overarching AdcR regulon. 48We have additionally utilized a 2D-NMR approach to analyze the secreted metabolome and 49 have employed proteomic analysis to identify a role for these systems in the maintenance of 50 cellular metabolism. This study provides new information on how Streptococcus pneumoniae 51 responds and adapts to zinc-limiting conditions. 52 53