California Institute of Technology

David K Romney

Sabine Brinkmann-Chen

Andrew Richard Buller

Javier Murciano Calles

Christina E Boville

Jori E Wehrmuller

Christopher K Prier

Philipp Koch

Remkes A Scheele

Michael Herger

Paul Van Roye

Patrick J Almhjell

Michaela M Sieben

This disclosure relates to modified tryptophan synthase and more particularly to modified beta-subunits of tryptophan synthase. The disclosure further relates to cells expressing such modified subunits and methods of producing non-canonical amino acids.

Engineered synthase for production of tryptophan derivatives and intransigent substrates

The present disclosure provides methods for preparing β-substituted tryptophan compounds. The methods include: combining i) an unsubstituted indole or a substituted indole, ii) a β-substituted serine, and iii) a tryptophan synthase β-subunit (i.e., a TrpB); and maintaining the resulting mixture under conditions sufficient to form the β-substituted tryptophan. The TrpB contains at least one amino acid mutation which promotes formation of an amino-acrylate intermediate. New TrpB variants and new β-substituted tryptophan analogs are also described.

Methods and enzyme catalysts for the synthesis of non-canonical amino acids

Engineered beta-subunit of tryptophan synthase for production of non-canonical amino acids

The present disclosure provides methods for preparing &#x3b2;-substituted tryptophan compounds. The methods include: combining i) an unsubstituted indole or a substituted indole, ii) a &#x3b2;-substituted serine, and iii) a tryptophan synthase &#x3b2;-subunit (i.e., a TrpB); and maintaining the resulting mixture under conditions sufficient to form the &#x3b2;-substituted tryptophan. The TrpB contains at least one amino acid mutation which promotes formation of an amino-acrylate intermediate. New TrpB variants and new &#x3b2;-substituted tryptophan analogs are also described.

The present disclosure provides methods for preparing tryptophans and tryptophan derivatives. The methods include: combining i) an indole substrate or azulene substrate, ii) a serine substrate, and iii) an engineered tryptophan synthase &#x3b2;-subunit (TrpB); and maintaining the resulting mixture under conditions sufficient to form the product compound. The engineered TrpB comprises a PLP binding loop mutation, a helix 1 mutation, a strand 7-8 mutation, or a combination thereof. New TrpB variants are also described.

Method for the synthesis of tryptophan analogs in aqueous solvents at reduced temperatures

Beta-substituted non-canonical amino acids

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Pasadena, CA, United States of America

David K Romney