Recent advances in biosynthesis of non-canonical amino acids and their potentials in strain engineering

Non-canonical amino acids (ncAAs), as derivatives of canonical amino acids (cAAs), when specifically incorporated into proteins, could enrich protein functions. Currently, ncAAs mostly depend on chemical synthesis; however, biosynthesis of ncAAs could solve the problems of low transmembrane transpor...

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Main Authors: Zhen Hou, Junkai Tuo, Xiaoyan Ma, Yi-Xin Huo
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Results in Engineering
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Online Access:http://www.sciencedirect.com/science/article/pii/S259012302401884X
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author Zhen Hou
Junkai Tuo
Xiaoyan Ma
Yi-Xin Huo
author_facet Zhen Hou
Junkai Tuo
Xiaoyan Ma
Yi-Xin Huo
author_sort Zhen Hou
collection DOAJ
description Non-canonical amino acids (ncAAs), as derivatives of canonical amino acids (cAAs), when specifically incorporated into proteins, could enrich protein functions. Currently, ncAAs mostly depend on chemical synthesis; however, biosynthesis of ncAAs could solve the problems of low transmembrane transport efficiency and potential toxicity of exogenously added ncAAs. Moreover, the biosynthesis of ncAAs is eco-friendly and economical. In this article, we firstly reviewed recent advances in the biosynthesis strategies of ncAAs, including hijacking the biosynthesis pathways of cAAs, deriving ncAAs from cAAs, and de novo biosynthesis of ncAAs, from the advantages, shortcomings, and potentials of these three strategies. Secondly, we discussed the applications of ncAAs in bacterial-based therapeutics, whole-cell biocatalysts, and biosafety. Finally, we provide guidance for the improvement of ncAAs biosynthesis and put forward perspectives on applying ncAAs in strain engineering. This work will promote the in situ synthesis of ncAAs modified proteins and unleash the potentials of ncAAs in strain engineering.
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publishDate 2025-03-01
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series Results in Engineering
spelling doaj-art-326aaaa57f0340fa83f13e3f56d7db1b2025-08-20T02:52:08ZengElsevierResults in Engineering2590-12302025-03-012510364110.1016/j.rineng.2024.103641Recent advances in biosynthesis of non-canonical amino acids and their potentials in strain engineeringZhen Hou0Junkai Tuo1Xiaoyan Ma2Yi-Xin Huo3Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, PR ChinaKey Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, PR ChinaKey Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China; Tangshan Research Institute, Beijing Institute of Technology, Hebei 063000, PR China; Center for Future Foods, Muyuan Laboratory, 110 ShangdingRoad, Zhengzhou, Henan Province 450016, PR China; Corresponding author at: Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China.Department of gastroenterology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China; Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China; Tangshan Research Institute, Beijing Institute of Technology, Hebei 063000, PR China; Center for Future Foods, Muyuan Laboratory, 110 ShangdingRoad, Zhengzhou, Henan Province 450016, PR ChinaNon-canonical amino acids (ncAAs), as derivatives of canonical amino acids (cAAs), when specifically incorporated into proteins, could enrich protein functions. Currently, ncAAs mostly depend on chemical synthesis; however, biosynthesis of ncAAs could solve the problems of low transmembrane transport efficiency and potential toxicity of exogenously added ncAAs. Moreover, the biosynthesis of ncAAs is eco-friendly and economical. In this article, we firstly reviewed recent advances in the biosynthesis strategies of ncAAs, including hijacking the biosynthesis pathways of cAAs, deriving ncAAs from cAAs, and de novo biosynthesis of ncAAs, from the advantages, shortcomings, and potentials of these three strategies. Secondly, we discussed the applications of ncAAs in bacterial-based therapeutics, whole-cell biocatalysts, and biosafety. Finally, we provide guidance for the improvement of ncAAs biosynthesis and put forward perspectives on applying ncAAs in strain engineering. This work will promote the in situ synthesis of ncAAs modified proteins and unleash the potentials of ncAAs in strain engineering.http://www.sciencedirect.com/science/article/pii/S259012302401884XBiosynthesisEnzyme engineeringGenetic code expansionUnnatural amino acidsEngineered bacterial therapeutics
spellingShingle Zhen Hou
Junkai Tuo
Xiaoyan Ma
Yi-Xin Huo
Recent advances in biosynthesis of non-canonical amino acids and their potentials in strain engineering
Results in Engineering
Biosynthesis
Enzyme engineering
Genetic code expansion
Unnatural amino acids
Engineered bacterial therapeutics
title Recent advances in biosynthesis of non-canonical amino acids and their potentials in strain engineering
title_full Recent advances in biosynthesis of non-canonical amino acids and their potentials in strain engineering
title_fullStr Recent advances in biosynthesis of non-canonical amino acids and their potentials in strain engineering
title_full_unstemmed Recent advances in biosynthesis of non-canonical amino acids and their potentials in strain engineering
title_short Recent advances in biosynthesis of non-canonical amino acids and their potentials in strain engineering
title_sort recent advances in biosynthesis of non canonical amino acids and their potentials in strain engineering
topic Biosynthesis
Enzyme engineering
Genetic code expansion
Unnatural amino acids
Engineered bacterial therapeutics
url http://www.sciencedirect.com/science/article/pii/S259012302401884X
work_keys_str_mv AT zhenhou recentadvancesinbiosynthesisofnoncanonicalaminoacidsandtheirpotentialsinstrainengineering
AT junkaituo recentadvancesinbiosynthesisofnoncanonicalaminoacidsandtheirpotentialsinstrainengineering
AT xiaoyanma recentadvancesinbiosynthesisofnoncanonicalaminoacidsandtheirpotentialsinstrainengineering
AT yixinhuo recentadvancesinbiosynthesisofnoncanonicalaminoacidsandtheirpotentialsinstrainengineering