Genetic Engineering Approaches for the Fermentative Production of Phenylglycines

Overview

Journal Appl Microbiol Biotechnol

Specialties Biomedical Engineering
Biotechnology
Microbiology

Date 2020 Feb 21

PMID 32078019

Citations 4

Authors

David Moosmann

Vladislav Mokeev

Andreas Kulik

Natalie Osipenkov

Susann Kocadinc

Regina Ort-Winklbauer

Franziska Handel

Oliver Hennrich

Jung-Won Youn

Georg A Sprenger

Yvonne Mast

Affiliations

Soon will be listed here.

Abstract

L-phenylglycine (L-Phg) is a rare non-proteinogenic amino acid, which only occurs in some natural compounds, such as the streptogramin antibiotics pristinamycin I and virginiamycin S or the bicyclic peptide antibiotic dityromycin. Industrially, more interesting than L-Phg is the enantiomeric D-Phg as it plays an important role in the fine chemical industry, where it is used as a precursor for the production of semisynthetic β-lactam antibiotics. Based on the natural L-Phg operon from Streptomyces pristinaespiralis and the stereo-inverting aminotransferase gene hpgAT from Pseudomonas putida, an artificial D-Phg operon was constructed. The natural L-Phg operon, as well as the artificial D-Phg operon, was heterologously expressed in different actinomycetal host strains, which led to the successful production of Phg. By rational genetic engineering of the optimal producer strains S. pristinaespiralis and Streptomyces lividans, Phg production could be improved significantly. Here, we report on the development of a synthetic biology-derived D-Phg pathway and the optimization of fermentative Phg production in actinomycetes by genetic engineering approaches. Our data illustrate a promising alternative for the production of Phgs.

Citing Articles

Biotransformation-coupled mutasynthesis for the generation of novel pristinamycin derivatives by engineering the phenylglycine residue.

Hennrich O, Weinmann L, Kulik A, Harms K, Klahn P, Youn J RSC Chem Biol. 2023; 4(12):1050-1063.

PMID: 38033732 PMC: 10685826. DOI: 10.1039/d3cb00143a.

Synthetic Biology Tools for Engineering Microbial Cells to Fight Superbugs.

Leon-Buitimea A, Balderas-Cisneros F, Garza-Cardenas C, Garza-Cervantes J, Morones-Ramirez J Front Bioeng Biotechnol. 2022; 10:869206.

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Improved l-phenylglycine synthesis by introducing an engineered cofactor self-sufficient system.

Wang P, Zhang X, Tao Y, Lv X, Cheng S, Liu C Synth Syst Biotechnol. 2022; 7(1):513-521.

PMID: 35024478 PMC: 8715069. DOI: 10.1016/j.synbio.2021.12.008.

Overview on Multienzymatic Cascades for the Production of Non-canonical α-Amino Acids.

Martinez-Rodriguez S, Torres J, Sanchez P, Ortega E Front Bioeng Biotechnol. 2020; 8:887.

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