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Investigating the Role of Class I Adenylate-Forming Enzymes in Natural Product Biosynthesis.

Publication ,  Journal Article
D'Ambrosio, HK; Derbyshire, ER
Published in: ACS chemical biology
January 2020

Adenylate-forming enzymes represent one of the most important enzyme classes in biology, responsible for the activation of carboxylate substrates for biosynthetic modifications. The byproduct of the adenylate-forming enzyme acetyl-CoA synthetase, acetyl-CoA, is incorporated into virtually every primary and secondary metabolic pathway. Modification of acetyl-CoA by an array of other adenylate-forming enzymes produces complex classes of natural products including nonribosomal peptides, polyketides, phenylpropanoids, lipopeptides, and terpenes. Adenylation domains possess a variety of unique structural and functional features that provide for such diversification in their resulting metabolites. As the number of organisms with sequenced genomes increases, more adenylate-forming enzymes are being identified, each with roles in metabolite production that have yet to be characterized. In this Review, we explore the broad role of class I adenylate-forming enzymes in the context of natural product biosynthesis and how they contribute to primary and secondary metabolism by focusing on important work conducted in the field. We highlight features of subclasses from this family that facilitate the production of structurally diverse metabolites, including those from noncanonical adenylation domains, and additionally discuss when biological roles for these compounds are known.

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Published In

ACS chemical biology

DOI

EISSN

1554-8937

ISSN

1554-8929

Publication Date

January 2020

Volume

15

Issue

1

Start / End Page

17 / 27

Related Subject Headings

  • Terpenes
  • Substrate Specificity
  • Structure-Activity Relationship
  • Protein Conformation
  • Polyketides
  • Peptides
  • Organic Chemistry
  • Metabolome
  • Metabolic Networks and Pathways
  • Coenzyme A Ligases
 

Citation

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D’Ambrosio, H. K., & Derbyshire, E. R. (2020). Investigating the Role of Class I Adenylate-Forming Enzymes in Natural Product Biosynthesis. ACS Chemical Biology, 15(1), 17–27. https://doi.org/10.1021/acschembio.9b00865
D’Ambrosio, Hannah K., and Emily R. Derbyshire. “Investigating the Role of Class I Adenylate-Forming Enzymes in Natural Product Biosynthesis.ACS Chemical Biology 15, no. 1 (January 2020): 17–27. https://doi.org/10.1021/acschembio.9b00865.
D’Ambrosio HK, Derbyshire ER. Investigating the Role of Class I Adenylate-Forming Enzymes in Natural Product Biosynthesis. ACS chemical biology. 2020 Jan;15(1):17–27.
D’Ambrosio, Hannah K., and Emily R. Derbyshire. “Investigating the Role of Class I Adenylate-Forming Enzymes in Natural Product Biosynthesis.ACS Chemical Biology, vol. 15, no. 1, Jan. 2020, pp. 17–27. Epmc, doi:10.1021/acschembio.9b00865.
D’Ambrosio HK, Derbyshire ER. Investigating the Role of Class I Adenylate-Forming Enzymes in Natural Product Biosynthesis. ACS chemical biology. 2020 Jan;15(1):17–27.
Journal cover image

Published In

ACS chemical biology

DOI

EISSN

1554-8937

ISSN

1554-8929

Publication Date

January 2020

Volume

15

Issue

1

Start / End Page

17 / 27

Related Subject Headings

  • Terpenes
  • Substrate Specificity
  • Structure-Activity Relationship
  • Protein Conformation
  • Polyketides
  • Peptides
  • Organic Chemistry
  • Metabolome
  • Metabolic Networks and Pathways
  • Coenzyme A Ligases