De Novo Production of Xanthohumol by a Metabolically Engineered Escherichia coli.

IF 3.9 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

ACS Synthetic Biology Pub Date : 2025-09-25 DOI:10.1021/acssynbio.5c00221

Daniela Gomes, Joana Santos, Armando Venâncio, Joana L Rodrigues, Nigel S Scrutton, Ligia R Rodrigues

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引用次数: 0

Abstract

Xanthohumol is a prenylflavonoid from hops with relevant bioactivities. Microbial production has emerged as a sustainable and potentially economic solution to produce it. Herein, we constructed a pathway for the de novo production of xanthohumol in Escherichia coli. Since the xanthohumol pathway depends on the availability of dimethylallyl pyrophosphate (DMAPP) and S-adenosylmethionine (SAM), SAM synthase (metK) was integrated into the genome of E. coli strains with previously engineered DMAPP pathways. Eleven prenyltransferases (PT) and the O-methyltransferase (OMT) from Humulus lupulus (HlOMT1) were tested. E. coli M-PAR-121:BlIDI:metK, constructed by integrating metK into the E. coli strain with integration of isopentenyl diphosphate isomerase (IDI) from Bacillus licheniformis (E. coli M-PAR-121:BlIDI) and expressing CdpC3PT from Neosartorya fischeri and HlOMT1 in combination with the naringenin chalcone pathway, was the best producer. This strain was able to produce 7.3 mg/L of desmethylxanthohumol and 5.3 mg/L of xanthohumol in the bioreactor, representing the first report of de novo production of xanthohumol in E. coli.

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利用代谢工程大肠杆菌从头生产黄腐酚。

黄腐酚是一种从啤酒花中提取的烯丙基类黄酮，具有一定的生物活性。微生物生产已经成为一种可持续的、潜在的经济解决方案。在此，我们构建了一条在大肠杆菌中重新生产黄腐酚的途径。由于黄腐酚途径依赖于二甲基丙烯基磷酸（DMAPP）和s -腺苷甲硫氨酸（SAM）的可用性，SAM合成酶（metK）被整合到具有先前设计的DMAPP途径的大肠杆菌菌株的基因组中。对葎草11种戊烯基转移酶（PT）和o -甲基转移酶（OMT）进行了检测。结合地衣芽孢杆菌（e.c oli M-PAR-121:BlIDI）的异戊烯基二磷酸异构酶（IDI）将metK整合到大肠杆菌（e.c oli M-PAR-121:BlIDI）中，并结合柚皮素查尔酮途径表达新树属（Neosartorya fischeri）和HlOMT1中的CdpC3PT，构建出的大肠杆菌M-PAR-121:BlIDI:metK的最佳产菌。该菌株在生物反应器中能够产生7.3 mg/L的去甲基黄腐酚和5.3 mg/L的黄腐酚，这是首次报道在大肠杆菌中重新生产黄腐酚。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Synthetic Biology 生物-

CiteScore

8.00

自引率

10.60%

发文量

380

审稿时长

6-12 weeks

期刊介绍： The journal is particularly interested in studies on the design and synthesis of new genetic circuits and gene products; computational methods in the design of systems; and integrative applied approaches to understanding disease and metabolism. Topics may include, but are not limited to: Design and optimization of genetic systems Genetic circuit design and their principles for their organization into programs Computational methods to aid the design of genetic systems Experimental methods to quantify genetic parts, circuits, and metabolic fluxes Genetic parts libraries: their creation, analysis, and ontological representation Protein engineering including computational design Metabolic engineering and cellular manufacturing, including biomass conversion Natural product access, engineering, and production Creative and innovative applications of cellular programming Medical applications, tissue engineering, and the programming of therapeutic cells Minimal cell design and construction Genomics and genome replacement strategies Viral engineering Automated and robotic assembly platforms for synthetic biology DNA synthesis methodologies Metagenomics and synthetic metagenomic analysis Bioinformatics applied to gene discovery, chemoinformatics, and pathway construction Gene optimization Methods for genome-scale measurements of transcription and metabolomics Systems biology and methods to integrate multiple data sources in vitro and cell-free synthetic biology and molecular programming Nucleic acid engineering.