Recent Advances of Diels-Alderases Involved in Natural Product Biosynthesis

Overview

Journal J Antibiot (Tokyo)

Specialties Infectious Diseases
Pharmacology

Date 2016 Jun 16

PMID 27301662

Citations 41

Authors

Atsushi Minami

Hideaki Oikawa

Affiliations

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Abstract

Frequent occurrence of [4+2] adducts in the secondary metabolites suggested involvement of Diels-Alderases (DAases) in their biosynthesis. However, a limited number of DAases were reported before early 2000s. Advancements in whole-genome sequencing and searching tool of the biosynthetic gene clusters of the secondary metabolites facilitate the identification of plausible DAases. Thus, during past 5 years, nine DAases have been characterized by genetic and biochemical analyses. These include a detailed functional analysis of SpnF that solely catalyzes [4+2] cycloaddition, a structural analysis of spirotetramate-forming enzyme PyrI4 complexed with the corresponding cycloadduct, and DAases catalyzing decalin formation and macrocyclic pyridine formation. Together with decalin-forming enzymes and macrocyclic pyridine-forming enzymes, these results provided sufficient data to discuss catalytic mechanism of DAases and nature's strategy for molecular diversification of linear chain intermediates derived from polyketide and ribosomal peptide biosynthetic machinery.

Citing Articles

Advances on the biosynthesis of pyridine rings.

Portero C, Han Y, Marchan-Rivadeneira M Eng Microbiol. 2024; 3(2):100064.

PMID: 39629243 PMC: 11611018. DOI: 10.1016/j.engmic.2022.100064.

Delineation of the complete reaction cycle of a natural Diels-Alderase.

Maschio L, Back C, Alnawah J, Bowen J, Johns S, Mbatha S Chem Sci. 2024; 15(29):11572-11583.

PMID: 39055018 PMC: 11268479. DOI: 10.1039/d4sc02908a.

Interrogation of an Enzyme Library Reveals the Catalytic Plasticity of Naturally Evolved [4+2] Cyclases.

Zorn K, Back C, Barringer R, Chadimova V, Manzo-Ruiz M, Mbatha S Chembiochem. 2023; 24(14):e202300382.

PMID: 37305956 PMC: 10946715. DOI: 10.1002/cbic.202300382.

Enzymatic Decalin Formation in Natural Product Biosynthesis.

Ohashi M, Tan D, Lu J, Jamieson C, Kanayama D, Zhou J J Am Chem Soc. 2023; 145(6):3301-3305.

PMID: 36723171 PMC: 9931682. DOI: 10.1021/jacs.2c12854.

What Drives Chorismate Mutase to Top Performance? Insights from a Combined and Study.

Thorbjornsrud H, Bressan L, Khatanbaatar T, Carrer M, Wurth-Roderer K, Cordara G Biochemistry. 2023; 62(3):782-796.

PMID: 36705397 PMC: 9910054. DOI: 10.1021/acs.biochem.2c00635.

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