Optimization of the l-tyrosine metabolic pathway in Saccharomyces cerevisiae by analyzing p-coumaric acid production
Artikel i vetenskaplig tidskrift, 2020

In this study, we applied a series of genetic modifications to wild-type S. cerevisiae strain BY4741 to address the bottlenecks in the l-tyrosine pathway. A tyrosine ammonia-lyase (TAL) gene from Rhodobacter capsulatus, which can catalyze conversion of l-tyrosine into p-coumaric acid, was overexpressed to facilitate the analysis of l-tyrosine and test the strain's capability to synthesize heterologous derivatives. First, we enhanced the supply of precursors by overexpressing transaldolase gene TAL1, enolase II gene ENO2, and pentafunctional enzyme gene ARO1 resulting in a 1.55-fold increase in p-coumaric acid production. Second, feedback inhibition of 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase and chorismate mutase was relieved by overexpressing the mutated feedback-resistant ARO4(K229L) and ARO7(G141S), and a 3.61-fold improvement of p-coumaric acid production was obtained. Finally, formation of byproducts was decreased by deleting pyruvate decarboxylase gene PDC5 and phenylpyruvate decarboxylase gene ARO10, and p-coumaric acid production was increased 2.52-fold. The best producer-when TAL1, ENO2, ARO1, ARO4(K229L), ARO7(G141S), and TAL were overexpressed, and PDC5 and ARO10 were deleted-increased p-coumaric acid production by 14.08-fold (from 1.4 to 19.71 mg L-1). Our study provided a valuable insight into the optimization of l-tyrosine metabolic pathway.

Metabolic engineering

p-Coumaric acid

Saccharomyces cerevisiae

L-Tyrosine

Författare

Yuanzi Li

Nankai University

Jiwei Mao

Chalmers, Biologi och bioteknik, Systembiologi

Xiaofei Song

Nankai University

Yuzhen Wu

Nankai University

Miao Cai

Nankai University

Hesuiyuan Wang

Nankai University

Quanli Liu

Chalmers, Biologi och bioteknik, Systembiologi

Xiuming Zhang

Nankai University

Yanling Bai

Nankai University

Haijin Xu

Nankai University

Mingqiang Qiao

Nankai University

3 Biotech

2190-572X (ISSN) 2190-5738 (eISSN)

Vol. 10 6 258

Ämneskategorier

Mikrobiologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

Mikrobiologi inom det medicinska området

DOI

10.1007/s13205-020-02223-3

PubMed

32550099

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Senast uppdaterat

2020-06-30