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Engineered Holo TrpB from Pyrococcus furiosus, PfTrpB7E6 with (2S,3S)-isopropylserine bound as the external aldimineEngineered Holo TrpB from Pyrococcus furiosus, PfTrpB7E6 with (2S,3S)-isopropylserine bound as the external aldimine
Structural highlights
Function[TRPB1_PYRFU] The beta subunit is responsible for the synthesis of L-tryptophan from indole and L-serine (By similarity). Publication Abstract from PubMedNon-canonical amino acids (ncAAs) with dual stereocenters at the alpha and beta positions are valuable precursors to natural products and therapeutics. Despite the potential applications of such bioactive beta-branched ncAAs, their availability is limited due to the inefficiency of the multi-step methods used to prepare them. Here we report a stereoselective biocatalytic synthesis of beta-branched tryptophan analogs using an engineered variant of Pyrococcus furiosus tryptophan synthase (PfTrpB), PfTrpB7E6. PfTrpB7E6 is the first biocatalyst to synthesize bulky beta-branched tryptophan analogs in a single step, with demonstrated access to 27 ncAAs. The molecular basis for the efficient catalysis and broad substrate tolerance of PfTrpB7E6 was explored through X-ray crystallography and UV-visible light spectroscopy, which revealed that a combination of active-site and remote mutations increase the abundance and persistence of a key reactive intermediate. PfTrpB7E6 provides an operationally simple and environmentally benign platform for preparation of beta-branched tryptophan building blocks. Engineered biosynthesis of beta-alkyl tryptophan analogs.,Boville CE, Scheele RA, Koch P, Brinkmann-Chen S, Buller AR, Arnold FH Angew Chem Int Ed Engl. 2018 Sep 14. doi: 10.1002/anie.201807998. PMID:30215880[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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