Accessing Nature’s diversity through metabolic engineering and synthetic biology [version 1; referees: 2 approved]
In this perspective, we highlight recent examples and trends in metabolic engineering and synthetic biology that demonstrate the synthetic potential of enzyme and pathway engineering for natural product discovery. In doing so, we introduce natural paradigms of secondary metabolism whereby simple car...
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doaj-77dcb96595694d9592496897b5617e5c2020-11-25T03:24:20ZengF1000 Research LtdF1000Research2046-14022016-03-01510.12688/f1000research.7311.17879Accessing Nature’s diversity through metabolic engineering and synthetic biology [version 1; referees: 2 approved]Jason R. King0Steven Edgar1Kangjian Qiao2Gregory Stephanopoulos3Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USADepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USADepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USADepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USAIn this perspective, we highlight recent examples and trends in metabolic engineering and synthetic biology that demonstrate the synthetic potential of enzyme and pathway engineering for natural product discovery. In doing so, we introduce natural paradigms of secondary metabolism whereby simple carbon substrates are combined into complex molecules through “scaffold diversification”, and subsequent “derivatization” of these scaffolds is used to synthesize distinct complex natural products. We provide examples in which modern pathway engineering efforts including combinatorial biosynthesis and biological retrosynthesis can be coupled to directed enzyme evolution and rational enzyme engineering to allow access to the “privileged” chemical space of natural products in industry-proven microbes. Finally, we forecast the potential to produce natural product-like discovery platforms in biological systems that are amenable to single-step discovery, validation, and synthesis for streamlined discovery and production of biologically active agents.http://f1000research.com/articles/5-397/v1Antimicrobials & Drug ResistanceBiocatalysisCancer TherapeuticsDrug Discovery & DesignGenomicsMicrobial Evolution & GenomicsMolecular PharmacologySmall Molecule Chemistry |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jason R. King Steven Edgar Kangjian Qiao Gregory Stephanopoulos |
spellingShingle |
Jason R. King Steven Edgar Kangjian Qiao Gregory Stephanopoulos Accessing Nature’s diversity through metabolic engineering and synthetic biology [version 1; referees: 2 approved] F1000Research Antimicrobials & Drug Resistance Biocatalysis Cancer Therapeutics Drug Discovery & Design Genomics Microbial Evolution & Genomics Molecular Pharmacology Small Molecule Chemistry |
author_facet |
Jason R. King Steven Edgar Kangjian Qiao Gregory Stephanopoulos |
author_sort |
Jason R. King |
title |
Accessing Nature’s diversity through metabolic engineering and synthetic biology [version 1; referees: 2 approved] |
title_short |
Accessing Nature’s diversity through metabolic engineering and synthetic biology [version 1; referees: 2 approved] |
title_full |
Accessing Nature’s diversity through metabolic engineering and synthetic biology [version 1; referees: 2 approved] |
title_fullStr |
Accessing Nature’s diversity through metabolic engineering and synthetic biology [version 1; referees: 2 approved] |
title_full_unstemmed |
Accessing Nature’s diversity through metabolic engineering and synthetic biology [version 1; referees: 2 approved] |
title_sort |
accessing nature’s diversity through metabolic engineering and synthetic biology [version 1; referees: 2 approved] |
publisher |
F1000 Research Ltd |
series |
F1000Research |
issn |
2046-1402 |
publishDate |
2016-03-01 |
description |
In this perspective, we highlight recent examples and trends in metabolic engineering and synthetic biology that demonstrate the synthetic potential of enzyme and pathway engineering for natural product discovery. In doing so, we introduce natural paradigms of secondary metabolism whereby simple carbon substrates are combined into complex molecules through “scaffold diversification”, and subsequent “derivatization” of these scaffolds is used to synthesize distinct complex natural products. We provide examples in which modern pathway engineering efforts including combinatorial biosynthesis and biological retrosynthesis can be coupled to directed enzyme evolution and rational enzyme engineering to allow access to the “privileged” chemical space of natural products in industry-proven microbes. Finally, we forecast the potential to produce natural product-like discovery platforms in biological systems that are amenable to single-step discovery, validation, and synthesis for streamlined discovery and production of biologically active agents. |
topic |
Antimicrobials & Drug Resistance Biocatalysis Cancer Therapeutics Drug Discovery & Design Genomics Microbial Evolution & Genomics Molecular Pharmacology Small Molecule Chemistry |
url |
http://f1000research.com/articles/5-397/v1 |
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