Short chain dehydrogenase; part of the gene cluster that mediates the biosynthesis of pleuromutilin, a tricyclic diterpene showing antibacterial properties (Ref.1). The geranylgeranyl diphosphate (GGPP) synthase ple4 catalyzes the first step in pleuromutilin biosynthesis (Ref.1). GGPP is then substrate of the premutilin synthase (PS) ple3 to yield premutilin (Ref.1). Premutilin synthase is a bifunctional enzyme composed of the fusion of a class II diterpene cyclase (DTC) and a class I diterpene synthase (DTS), with the corresponding domains and active sites containing characteristic aspartate-rich motifs (By similarity). GGPP is first converted to mutildienyl-diphosphate (MPP) at the class II DTC site (By similarity). MPP is subsequently further cyclized at the class I DTS site, followed by a 1,5-hydride shift and addition of water prior to terminating deprotonation, to yield premutilin (By similarity). The cytochrome P450 monooxygenases ple5 and ple6 hydroxylate premutilin at C-11 and C-3, respectively, producing 11-hydroxypremutilin and 3-hydroxypremutilin (Ref.1). The combination of the actions of both ple5 and ple6 leads to the production of 3,11-dihydroxypremutilin (Ref.1). The short chain dehydrogenase ple7 further converts 3,11-dihydroxypremutilin into mutilin (Ref.1). The acetyltransferase ple2 then acetylates mutilin to produce 14-O-acetylmutilin (Ref.1). Finally, the cytochrome P450 monooxygenase ple1 catalyzes hydroxylation on the alpha position of the acetyl side chain of 14-O-acetylmutilin to yield pleuromutilin (Ref.1). Secondary metabolite biosynthesis; terpenoid biosynthesis. Belongs to the short-chain dehydrogenases/reductases (SDR) family.