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7N4W

Complex structure of ROTU4 with rotundine

Summary for 7N4W
Entry DOI10.2210/pdb7n4w/pdb
Related7N4Z 7N53 7N54
DescriptorROTU4, SULFATE ION, GLYCEROL, ... (5 entities in total)
Functional Keywordstranscription factor, protein engineering, specificity, synthetic biology, transcription
Biological sourceSalmonella enterica subsp. enterica serovar Typhimurium str. 14028S
Total number of polymer chains1
Total formula weight22688.97
Authors
Kim, W.,Zhang, Y. (deposition date: 2021-06-04, release date: 2022-06-29, Last modification date: 2023-10-18)
Primary citationd'Oelsnitz, S.,Kim, W.,Burkholder, N.T.,Javanmardi, K.,Thyer, R.,Zhang, Y.,Alper, H.S.,Ellington, A.D.
Using fungible biosensors to evolve improved alkaloid biosyntheses.
Nat.Chem.Biol., 18:981-989, 2022
Cited by
PubMed Abstract: A key bottleneck in the microbial production of therapeutic plant metabolites is identifying enzymes that can improve yield. The facile identification of genetically encoded biosensors can overcome this limitation and become part of a general method for engineering scaled production. We have developed a combined screening and selection approach that quickly refines the affinities and specificities of generalist transcription factors; using RamR as a starting point, we evolve highly specific (>100-fold preference) and sensitive (half-maximum effective concentration (EC) < 30 μM) biosensors for the alkaloids tetrahydropapaverine, papaverine, glaucine, rotundine and noscapine. High-resolution structures reveal multiple evolutionary avenues for the malleable effector-binding site and the creation of new pockets for different chemical moieties. These sensors further enabled the evolution of a streamlined pathway for tetrahydropapaverine, a precursor to four modern pharmaceuticals, collapsing multiple methylation steps into a single evolved enzyme. Our methods for evolving biosensors enable the rapid engineering of pathways for therapeutic alkaloids.
PubMed: 35799063
DOI: 10.1038/s41589-022-01072-w
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.64 Å)
Structure validation

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