Literature summary for 1.14.13.38 extracted from

Herbst, E.; Lee, A.; Tang, Y.; Snyder, S.; Cornish, V.
Heterologous catalysis of the final steps of tetracycline biosynthesis by Saccharomyces cerevisiae (2021), ACS Chem. Biol., 16, 1425-1434 .

Search for more literature for 1.14.13.38

Application

Application	Comment	Organism
synthesis	biosynthesis of tetracycline from anhydrotetracycline in Saccharomyces cerevisiae heterologously expressing the anhydrotetracycline hydroxylase OxyS, the dehydrotetracycline reductase CtcM, and the F420 reductase FNO from three bacterial hosts. This biosynthesis of tetracycline is enabled by OxyS performing just one hydroxylation step in S. cerevisiae	Streptomyces rimosus subsp. rimosus

Cloned(Commentary)

Cloned (Comment)	Organism
gene oxyS, functional recombinant overexpression of C-terminally FLAG-tagged enzyme in Saccharomyces cerevisiae from plasmid pSP-G1 resulting in biosynthesis of dehydrotetracycline from anhydrotetracycline, functional coexpression with heterologous dehydrotetracycline reductase CtcM, and the F420 reductase FNO	Streptomyces sp.

Protein Variants

Protein Variants	Comment	Organism
additional information	recombinant overexpression of gene oxySin Saccharomyces cerevisiae, functional coexpression with heterologous dehydrotetracycline reductase CtcM, and the F420 reductase FNO. Biosynthesis of tetracycline is enabled by OxyS performing just one hydroxylation step in Saccharomyces cerevisiae despite its previous characterization as a double hydroxylase. This single hydroxylation enables the purification and structural characterization of a hypothetical intermediate in oxytetracycline biosynthesis that can explain structural differences between oxytetracycline and chlortetracycline. Using the alternative enzyme CtcM from the chlortetracycline pathway instead of OxyR yields in vitro an increased ratio of tetracycline to oxytetracycline. A unique cofactor to the last steps of the tetracyclines' biosynthesis that is not native to Saccharomyces cerevisiae is cofactor F420, a lactyl oligoglutamate phosphodiester derivative of 7,8-didemethyl-8-hydroxy-5-deazariboflavin (Fo). Fo is much more synthetically accessible than F420. Fo can replace F420 in tetracycline biosynthesis. Three F420 reductase candidates from Mycobacterium tuberculosis, Archaeoglobus fulgidus, and Streptomyces griseus are explored, and the enzyme from Archaeoglobus fulgidus is chosen. Method development and evaluation, method optimization, overview	Streptomyces sp.

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
anhydrotetracycline + NADPH + H+ + O2	Streptomyces sp.	-	12-dehydrotetracycline + NADP+ + H2O	-	?

Organism

Organism	UniProt	Comment	Textmining
Streptomyces rimosus subsp. rimosus	L8EUQ6	cf. EC 1.14.13.234	-
Streptomyces rimosus subsp. rimosus DSM 40260	L8EUQ6	cf. EC 1.14.13.234	-
Streptomyces sp.	-	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
anhydrotetracycline + NADPH + H+ + O2	-	Streptomyces sp.	12-dehydrotetracycline + NADP+ + H2O	-	?
anhydrotetracycline + NADPH + H+ + O2	-	Streptomyces rimosus subsp. rimosus	5a,11a-dehydrotetracycline + NADP+ + H2O	-	?
anhydrotetracycline + NADPH + H+ + O2	-	Streptomyces rimosus subsp. rimosus DSM 40260	5a,11a-dehydrotetracycline + NADP+ + H2O	-	?

Synonyms

Synonyms	Comment	Organism
anhydrotetracycline hydroxylase	-	Streptomyces sp.
oxyS	-	Streptomyces sp.

Cofactor

Cofactor	Comment	Organism	Structure
NADPH	-	Streptomyces sp.

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Release 2023.1 (January 2023)