Emerging molecular biology tools and strategies for engineering natural product biosynthesis

Wei Xu; Evaldas Klumbys; Ee Lui Ang; Huimin Zhao

doi:10.1016/j.mec.2019.e00108

Emerging molecular biology tools and strategies for engineering natural product biosynthesis

Wei Xu, Evaldas Klumbys, Ee Lui Ang, Huimin Zhao

Research output: Contribution to journal › Review article › peer-review

Abstract

Natural products and their related derivatives play a significant role in drug discovery and have been the inspiration for the design of numerous synthetic bioactive compounds. With recent advances in molecular biology, numerous engineering tools and strategies were established to accelerate natural product synthesis in both academic and industrial settings. However, many obstacles in natural product biosynthesis still exist. For example, the native pathways are not appropriate for research or production; the key enzymes do not have enough activity; the native hosts are not suitable for high-level production. Emerging molecular biology tools and strategies have been developed to not only improve natural product titers but also generate novel bioactive compounds. In this review, we will discuss these emerging molecular biology tools and strategies at three main levels: enzyme level, pathway level, and genome level, and highlight their applications in natural product discovery and development.

Original language	English (US)
Article number	e00108
Journal	Metabolic Engineering Communications
Volume	10
DOIs	https://doi.org/10.1016/j.mec.2019.e00108
State	Published - Jun 2020

Keywords

Biosynthesis
Enzyme engineering
Metabolic engineering
Natural products
Pathway engineering
Synthetic biology

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biomedical Engineering

Online availability

10.1016/j.mec.2019.e00108

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title = "Emerging molecular biology tools and strategies for engineering natural product biosynthesis",

abstract = "Natural products and their related derivatives play a significant role in drug discovery and have been the inspiration for the design of numerous synthetic bioactive compounds. With recent advances in molecular biology, numerous engineering tools and strategies were established to accelerate natural product synthesis in both academic and industrial settings. However, many obstacles in natural product biosynthesis still exist. For example, the native pathways are not appropriate for research or production; the key enzymes do not have enough activity; the native hosts are not suitable for high-level production. Emerging molecular biology tools and strategies have been developed to not only improve natural product titers but also generate novel bioactive compounds. In this review, we will discuss these emerging molecular biology tools and strategies at three main levels: enzyme level, pathway level, and genome level, and highlight their applications in natural product discovery and development.",

keywords = "Biosynthesis, Enzyme engineering, Metabolic engineering, Natural products, Pathway engineering, Synthetic biology",

author = "Wei Xu and Evaldas Klumbys and Ang, {Ee Lui} and Huimin Zhao",

note = "Funding Information: We gratefully acknowledge financial support from the National Institutes of Health (GM077596 and AI144967 to H.Z.), the A*STAR Visiting Investigator Program (H.Z.), and the National Research Foundation, Singapore (NRF2017NRF-CRP001-044) (E.A.). Funding Information: We gratefully acknowledge financial support from the National Institutes of Health ( GM077596 and AI144967 to H.Z.), the A*STAR Visiting Investigator Program (H.Z.), and the National Research Foundation, Singapore ( NRF2017NRF-CRP001-044 ) (E.A.). Appendix A Publisher Copyright: {\textcopyright} 2019 The Authors",

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doi = "10.1016/j.mec.2019.e00108",

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AU - Xu, Wei

AU - Klumbys, Evaldas

AU - Ang, Ee Lui

AU - Zhao, Huimin

N1 - Funding Information: We gratefully acknowledge financial support from the National Institutes of Health (GM077596 and AI144967 to H.Z.), the A*STAR Visiting Investigator Program (H.Z.), and the National Research Foundation, Singapore (NRF2017NRF-CRP001-044) (E.A.). Funding Information: We gratefully acknowledge financial support from the National Institutes of Health ( GM077596 and AI144967 to H.Z.), the A*STAR Visiting Investigator Program (H.Z.), and the National Research Foundation, Singapore ( NRF2017NRF-CRP001-044 ) (E.A.). Appendix A Publisher Copyright: © 2019 The Authors

PY - 2020/6

Y1 - 2020/6

N2 - Natural products and their related derivatives play a significant role in drug discovery and have been the inspiration for the design of numerous synthetic bioactive compounds. With recent advances in molecular biology, numerous engineering tools and strategies were established to accelerate natural product synthesis in both academic and industrial settings. However, many obstacles in natural product biosynthesis still exist. For example, the native pathways are not appropriate for research or production; the key enzymes do not have enough activity; the native hosts are not suitable for high-level production. Emerging molecular biology tools and strategies have been developed to not only improve natural product titers but also generate novel bioactive compounds. In this review, we will discuss these emerging molecular biology tools and strategies at three main levels: enzyme level, pathway level, and genome level, and highlight their applications in natural product discovery and development.

AB - Natural products and their related derivatives play a significant role in drug discovery and have been the inspiration for the design of numerous synthetic bioactive compounds. With recent advances in molecular biology, numerous engineering tools and strategies were established to accelerate natural product synthesis in both academic and industrial settings. However, many obstacles in natural product biosynthesis still exist. For example, the native pathways are not appropriate for research or production; the key enzymes do not have enough activity; the native hosts are not suitable for high-level production. Emerging molecular biology tools and strategies have been developed to not only improve natural product titers but also generate novel bioactive compounds. In this review, we will discuss these emerging molecular biology tools and strategies at three main levels: enzyme level, pathway level, and genome level, and highlight their applications in natural product discovery and development.

KW - Biosynthesis

KW - Enzyme engineering

KW - Metabolic engineering

KW - Natural products

KW - Pathway engineering

KW - Synthetic biology

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Emerging molecular biology tools and strategies for engineering natural product biosynthesis

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