公开(公告)号：US12024731B2

公开(公告)日：2024-07-02

申请号：US17556555

申请日：2021-12-20

Applicant: California Institute of Technology

Inventor： Christina E. Boville ,  Sabine Brinkmann-Chen ,  Andrew R. Buller ,  David K. Romney ,  Christopher K. Prier ,  Philipp Koch ,  Remkes A. Scheele

IPC: C12N9/88 ,  C07K14/415 ,  C12P13/00 ,  C12P13/04 ,  C12P13/06 ,  C12P13/22 ,  C12N15/82

CPC classification number: C12P13/227 ,  C07K14/415 ,  C12N9/88 ,  C12P13/005 ,  C12P13/04 ,  C12P13/06 ,  C12N15/8254 ,  C12Y402/0102

Abstract: 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.

公开(公告)号：US11279959B2

公开(公告)日：2022-03-22

申请号：US16820538

申请日：2020-03-16

Applicant: California Institute of Technology

Inventor： Christina E. Boville ,  Sabine Brinkmann-Chen ,  Andrew R. Buller ,  David K. Romney ,  Christopher K. Prier ,  Philipp Koch ,  Remkes A. Scheele

IPC: C12N9/06 ,  C12N1/21 ,  C12P13/04 ,  C12P13/22 ,  C07K14/415 ,  C12P13/00 ,  C12P13/06 ,  C12N9/88 ,  C12N15/82

Abstract: 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.

公开(公告)号：US11879143B2

公开(公告)日：2024-01-23

申请号：US16691452

申请日：2019-11-21

Applicant: California Institute of Technology

Inventor： Andrew Richard Buller ,  Sabine Brinkmann-Chen ,  Michael Herger ,  David K. Romney ,  Javier Murciano Calles ,  Paul van Roye

IPC: C12P13/22 ,  C12N9/88 ,  C12P13/04

CPC classification number: C12P13/227 ,  C12N9/88 ,  C12P13/04 ,  C12Y402/0102

Abstract: 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.

公开(公告)号：US20220364130A1

公开(公告)日：2022-11-17

申请号：US17556555

申请日：2021-12-20

Applicant: California Institute of Technology

Inventor： Christina E. Boville ,  Sabine Brinkmann-Chen ,  Andrew R. Buller ,  David K. Romney ,  Christopher K. Prier ,  Philipp Koch ,  Remkes A. Scheele

IPC: C12P13/22 ,  C07K14/415 ,  C12P13/00 ,  C12P13/06 ,  C12P13/04 ,  C12N9/88

Abstract: 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.

公开(公告)号：US10513719B2

公开(公告)日：2019-12-24

申请号：US15094458

申请日：2016-04-08

Applicant: The California Institute of Technology

Inventor： Andrew Richard Buller ,  Sabine Brinkmann-Chen ,  Michael Herger ,  David K. Romney ,  Javier Murciano Calles ,  Paul van Roye

IPC: C12N9/88 ,  C12N1/21 ,  C12N15/60 ,  C12P13/22 ,  C12P13/04

Abstract: 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.

公开(公告)号：US20240175002A1

公开(公告)日：2024-05-30

申请号：US18530082

申请日：2023-12-05

Applicant: California Institute of Technology

Inventor： David K. Romney ,  Javier Murciano Calles ,  Jori E. Wehrmuller

IPC: C12N9/88 ,  C07D209/20 ,  C12P13/22

CPC classification number: C12N9/88 ,  C07D209/20 ,  C12P13/227 ,  C12Y402/0102

Abstract: 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.

公开(公告)号：US20220259581A1

公开(公告)日：2022-08-18

申请号：US17724390

申请日：2022-04-19

Applicant: California Institute of Technology

Inventor： David K. Romney ,  Javier Murciano Calles ,  Jori E. Wehrmuller

IPC: C12N9/88 ,  C07D209/20 ,  C12P13/22

Abstract: 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.

公开(公告)号：US20180057806A1

公开(公告)日：2018-03-01

申请号：US15685839

申请日：2017-08-24

Applicant: California Institute of Technology

Inventor： David K. Romney ,  Javier Murciano Calles ,  Jori E. Wehrmuller

IPC: C12N9/88 ,  C07D209/20 ,  C12P13/22

CPC classification number: C12N9/88 ,  C07D209/20 ,  C12P13/227 ,  C12Y402/0102

Abstract: 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.

公开(公告)号：US11332729B2

公开(公告)日：2022-05-17

申请号：US15685839

申请日：2017-08-24

Applicant: California Institute of Technology

Inventor： David K. Romney ,  Javier Murciano Calles ,  Jori E. Wehrmuller

IPC: C12N9/00 ,  C12N9/88 ,  C07D209/20 ,  C12P13/22

Abstract: 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.

公开(公告)号：US10752927B2

公开(公告)日：2020-08-25

申请号：US16290695

申请日：2019-03-01

Applicant: California Institute of Technology

Inventor： Christina E. Boville ,  David K. Romney ,  Patrick J. Almhjell ,  Michaela M. Sieben

IPC: C12P17/10 ,  C12N9/88

Abstract: 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 β-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.