4K2X

OxyS anhydrotetracycline hydroxylase from Streptomyces rimosus

Summary for 4K2X

• Entry DOI: 10.2210/pdb4k2x/pdb
• Descriptor: Polyketide oxygenase/hydroxylase, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: para-hydroxybenzoate hydroxylase fold, hydroxylase, fad binding, oxidoreductase, flavoprotein
• Biological source: Streptomyces rimosus
• Total number of polymer chains: 2
• Total formula weight: 114997.25

Authors

Wang, P.,Sawaya, M.R.,Tang, Y. (deposition date: 2013-04-09, release date: 2013-05-15, Last modification date: 2023-09-20)

Primary citation

Wang, P.,Bashiri, G.,Gao, X.,Sawaya, M.R.,Tang, Y.
Uncovering the Enzymes that Catalyze the Final Steps in Oxytetracycline Biosynthesis.
J.Am.Chem.Soc., 135:7138-7141, 2013

PubMed Abstract: Tetracyclines 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.

PubMed: 23621493
DOI: 10.1021/ja403516u

Experimental method

X-RAY DIFFRACTION (2.55 Å)