Dataset Information

Tryptophan Synthase: Biocatalyst Extraordinaire.

ABSTRACT: Tryptophan synthase (TrpS) has emerged as a paragon of noncanonical amino acid (ncAA) synthesis and is an ideal biocatalyst for synthetic and biological applications. TrpS catalyzes an irreversible, C-C bond-forming reaction between indole and serine to make l-tryptophan; native TrpS complexes possess fairly broad specificity for indole analogues, but are difficult to engineer to extend substrate scope or to confer other useful properties due to allosteric constraints and their heterodimeric structure. Directed evolution freed the catalytically relevant TrpS β-subunit (TrpB) from allosteric regulation by its TrpA partner and has enabled dramatic expansion of the enzyme's substrate scope. This review examines the long and storied career of TrpS from the perspective of its application in ncAA synthesis and biocatalytic cascades.

SUBMITTER: Watkins-Dulaney E

PROVIDER: S-EPMC7935429 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Tryptophan Synthase: Biocatalyst Extraordinaire.

Watkins-Dulaney Ella E Straathof Sabine S Arnold Frances F

Chembiochem : a European journal of chemical biology 20200922 1

Tryptophan synthase (TrpS) has emerged as a paragon of noncanonical amino acid (ncAA) synthesis and is an ideal biocatalyst for synthetic and biological applications. TrpS catalyzes an irreversible, C-C bond-forming reaction between indole and serine to make l-tryptophan; native TrpS complexes possess fairly broad specificity for indole analogues, but are difficult to engineer to extend substrate scope or to confer other useful properties due to allosteric constraints and their heterodimeric str ...[more]

PMID: 32677310

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Project description:BackgroundMicroorganisms and plants are able to produce tryptophan. Enzymes catalysing the last seven steps of tryptophan biosynthesis are encoded in the canonical trp operon. Among the trp genes are most frequently trpA and trpB, which code for the alpha and beta subunit of tryptophan synthase. In several prokaryotic genomes, two variants of trpB (named trpB1 or trpB2) occur in different combinations. The evolutionary history of these trpB genes is under debate.ResultsIn order to study the evolution of trp genes, completely sequenced archeal and bacterial genomes containing trpB were analysed. Phylogenetic trees indicated that TrpB sequences constitute four distinct groups; their composition is in agreement with the location of respective genes. The first group consisted exclusively of trpB1 genes most of which belonged to trp operons. Groups two to four contained trpB2 genes. The largest group (trpB2_o) contained trpB2 genes all located outside of operons. Most of these genes originated from species possessing an operon-based trpB1 in addition. Groups three and four pertain to trpB2 genes of those genomes containing exclusively one or two trpB2 genes, but no trpB1. One group (trpB2_i) consisted of trpB2 genes located inside, the other (trpB2_a) of trpB2 genes located outside the trp operon. TrpA and TrpB form a heterodimer and cooperate biochemically. In order to characterise trpB variants and stages of TrpA/TrpB cooperation in silico, several approaches were combined. Phylogenetic trees were constructed for all trp genes; their structure was assessed via bootstrapping. Alternative models of trpB evolution were evaluated with parsimony arguments. The four groups of trpB variants were correlated with archeal speciation. Several stages of TrpA/TrpB cooperation were identified and trpB variants were characterised. Most plausibly, trpB2 represents the predecessor of the modern trpB gene, and trpB1 evolved in an ancestral bacterium.ConclusionIn archeal genomes, several stages of trpB evolution, TrpA/TrpB cooperation, and operon formation can be observed. Thus, archeal trp genes may serve as a model system for studying the evolution of protein-protein interactions and operon formation.

Dataset Information

Tryptophan Synthase: Biocatalyst Extraordinaire.

Publications

Tryptophan Synthase: Biocatalyst Extraordinaire.

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