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Natural Product Enzymatic Assembly Lines: Novel Features
Author(s) -
Walsh Christopher T
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a147-e
Subject(s) - nonribosomal peptide , polyketide , natural product , depsipeptide , chemistry , polyketide synthase , monomer , thioester , enzyme , stereochemistry , biosynthesis , acyl carrier protein , combinatorial chemistry , biochemistry , organic chemistry , polymer
Thousands of polyketide and nonribosomal peptide natural products are assembled on multimodular enzymatic assembly lines. Natural product acyl chains grow as a series of thioester intermediates covalently tethered via phosphoantetheinyl arms to carrier protein domains, with initiation, elongation, and termination steps. Tailoring enzymes can act during chain growth on the assembly lines or in post assembly line modifications. Two on‐assembly line tailoring processes that diversify natural product scaffolds are: (1) introduction of beta branching in polyketides, and (2) depsipeptide formation in nonribosomal peptides by α‐hydroxy acid instead of α‐amino acid monomers to make ester rather than amide bonds. The polyketide beta branching arises by convergence of isoprenoid and polyketide enzymatic assembly linee machinery while the ester linkages in NRPs such as valinomycin and cereulide arise by in situ reductions of tethered αketo acid monomers