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Integrating the protein and metabolic engineering toolkits for next-generation chemical biosynthesis.

Authors
  • Pirie, Christopher M1
  • De Mey, Marjan
  • Jones Prather, Kristala L
  • Ajikumar, Parayil Kumaran
  • 1 Manus Biosynthesis Inc., Suite 102, 790 Memorial Drive, Cambridge, MA 02139, USA.
Type
Published Article
Journal
ACS Chemical Biology
Publisher
American Chemical Society
Publication Date
Apr 19, 2013
Volume
8
Issue
4
Pages
662–672
Identifiers
DOI: 10.1021/cb300634b
PMID: 23373985
Source
Medline
Language
English
License
Unknown

Abstract

Through microbial engineering, biosynthesis has the potential to produce thousands of chemicals used in everyday life. Metabolic engineering and synthetic biology are fields driven by the manipulation of genes, genetic regulatory systems, and enzymatic pathways for developing highly productive microbial strains. Fundamentally, it is the biochemical characteristics of the enzymes themselves that dictate flux through a biosynthetic pathway toward the product of interest. As metabolic engineers target sophisticated secondary metabolites, there has been little recognition of the reduced catalytic activity and increased substrate/product promiscuity of the corresponding enzymes compared to those of central metabolism. Thus, fine-tuning these enzymatic characteristics through protein engineering is paramount for developing high-productivity microbial strains for secondary metabolites. Here, we describe the importance of protein engineering for advancing metabolic engineering of secondary metabolism pathways. This pathway integrated enzyme optimization can enhance the collective toolkit of microbial engineering to shape the future of chemical manufacturing.

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