4k2x | pdb_00004k2x
OxyS anhydrotetracycline hydroxylase from Streptomyces rimosus
Structural highlights
FunctionOXYS_STRR1 Involved in the biosynthesis of the antibiotics oxytetracycline and tetracycline. OxyS starts by catalyzing the stereospecific hydroxylation of anhydrotetracycline at C(6) position to yield 5a,11a-dehydrotetracycline (12-dehydrotetracycline). If the released product is captured by OxyR, it is reduced to tetracycline. However, if the released product is recaptured by OxyS, it performs an additional hydroxylation at C(5), producing 5a,11a-dehydrooxytetracycline, which, following the action of OxyR becomes oxytetracycline.[1] Publication Abstract from PubMedTetracyclines are a group of natural products sharing a linearly fused four-ring scaffold, which is essential for their broad-spectrum antibiotic activities. Formation of the key precursor anhydrotetracycline 3 during oxytetracycline 1 biosynthesis has been previously characterized. However, the enzymatic steps that transform 3 into 1, including the additional hydroxylation at C5 and the final C5a-C11a reduction, have remained elusive. Here we report two redox enzymes, OxyS and OxyR, are sufficient to convert 3 to 1. OxyS catalyzes two sequential hydroxylations at C6 and C5 positions of 3 with opposite stereochemistry, while OxyR catalyzes the C5a-C11a reduction using F420 as a cofactor to produce 1. The crystal structure of OxyS was obtained to provide insights into the tandem C6- and C5-hydroxylation steps. The substrate specificities of OxyS and OxyR were shown to influence the relative ratio of 1 and tetracycline 2. Uncovering the Enzymes that Catalyze the Final Steps in Oxytetracycline Biosynthesis.,Wang P, Bashiri G, Gao X, Sawaya MR, Tang Y J Am Chem Soc. 2013 May 15;135(19):7138-7141. Epub 2013 May 1. PMID:23621493[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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