Fig. 1

Biosynthesis of oxytetracycline in Streptomyces rimosus. Biosynthesis of the oxytetracycline backbone is catalysed by a minimal PKS through successive decarboxylative Claisen-like condensations of eight malonyl-CoA extender units to the amidated starter unit malonamyl-CoA [91]. Subsequently, the intermediate is reduced and modified by cyclases and aromatases, yielding an entirely aromatized intermediate called pretetramide [14]. Pretetramide undergoes multiple tailoring reactions catalysed by oxygenases, methyltransferases, aminotransferases, and reductases to finally generate the fully functional oxytetracycline, which is characterized by four aromatic rings and a C2-amide group and is specific for the tetracycline class of antibiotics. Abbreviations: TCA, tricarboxylic acid; FAS, fatty acid synthesis; PGM, phosphoglucomutase; GLK, glucokinase; PGI, phosphoglucose isomerase; MDH, mannitol dehydrogenase; PFK1, phosphofructokinase 1, PDH, pyruvate dehydrogenase; ACC, acetyl-CoA carboxylase; KS, ketosynthase; CLF, chain length factor; ACP, acyl carrier protein; GAT, glutamine amidotransferase; OX, oxygenase; MT, methyltransferase; KR,: ketoreductase; CYC, cyclase; ARO, aromatase; MCAT, malonyl-CoA:ACP acyltransferase; AT, aminotransferase; REG, regulation; RES, resistance. The function of the enzymes encoded by oxyHO is not yet fully understood