High-yield production of β-arbutin by identifying and eliminating byproducts formation.
6-O-Acetylarbutin
Byproduct
Escherichia coli
Yield
β-Arbutin
Journal
Applied microbiology and biotechnology
ISSN: 1432-0614
Titre abrégé: Appl Microbiol Biotechnol
Pays: Germany
ID NLM: 8406612
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
01
02
2023
accepted:
23
07
2023
revised:
18
07
2023
medline:
9
10
2023
pubmed:
19
8
2023
entrez:
19
8
2023
Statut:
ppublish
Résumé
β-Arbutin is a plant-derived glycoside and widely used in cosmetic and pharmaceutical industries because of its safe and effective skin-lightening property as well as anti-oxidant, anti-microbial, and anti-inflammatory activities. In recent years, microbial fermentation has become a highly promising method for the production of β-arbutin. However, this method suffers from low titer and low yield, which has become the bottleneck for its widely industrial application. In this study, we used β-arbutin to demonstrate methods for improving yields for industrial-scale production in Escherichia coli. First, the supply of precursors phosphoenolpyruvate and uridine diphosphate glucose was improved, leading to a 4.6-fold increase in β-arbutin production in shaking flasks. The engineered strain produced 36.12 g/L β-arbutin with a yield of 0.11 g/g glucose in a 3-L bioreactor. Next, based on the substrate and product's structural similarity, an endogenous O-acetyltransferase was identified as responsible for 6-O-acetylarbutin formation for the first time. Eliminating the formation of byproducts, including 6-O-acetylarbutin, tyrosine, and acetate, resulted in an engineered strain producing 43.79 g/L β-arbutin with a yield of 0.22 g/g glucose in fed-batch fermentation. Thus, the yield increased twofold by eliminating byproducts formation. To the best of our knowledge, this is the highest titer and yield of β-arbutin ever reported, paving the way for the industrial production of β-arbutin. This study demonstrated a systematic strategy to alleviate undesirable byproduct accumulation and improve the titer and yield of target products. KEY POINTS: • A systematic strategy to improve titer and yield was showed • Genes responsible for 6-O-acetylarbutin formation were firstly identified • 43.79 g/L β-arbutin was produced in bioreactor, which is the highest titer so far.
Identifiants
pubmed: 37597019
doi: 10.1007/s00253-023-12706-x
pii: 10.1007/s00253-023-12706-x
doi:
Substances chimiques
Arbutin
C5INA23HXF
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6193-6204Subventions
Organisme : National Key Research and Development Program of China
ID : 2021YFC2100800
Organisme : National Natural Science Foundation of China
ID : 22078011
Organisme : National Natural Science Foundation of China
ID : 22238001
Organisme : Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project
ID : TSBICIP-KJGG-009
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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