Work

Structural insights into nonribosomal peptide enzymatic assembly lines

Year: 2009

Type: review

Abstract: Nonribosomal peptides have a variety of medicinal activities including activity as antibiotics, antitumor drugs, immunosuppressives, and toxins. Their biosynthesis on multimodular assembly lines as a series of covalently tethered thioesters, in turn covalently attached on pantetheinyl arms on carrier protein way stations, reflects similar chemical logic and protein machinery to fatty acid and polyketide biosynthesis. While structural information on excised or isolated catalytic adenylation (A), condensation (C), peptidyl carrier protein (PCP) and thioesterase (TE) domains had been gathered over the past decade, little was known about how the NRPS catalytic and carrier domains interact with each other both within and across elongation or termination modules. This Highlight reviews recent breakthrough achievements in both X-ray and NMR spectroscopic studies that illuminate the architecture of NRPS PCP domains, PCP-containing didomain-fragments and of a full termination module (C-A-PCP-TE).

Source: Natural Product Reports

DOI: 10.1039/b904543k

Authors: Alexander Koglin, Christopher T. Walsh

Institution: Harvard University

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Applied Microbiology and Biotechnology

Field: Immunology and Microbiology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences

Awards: G1561632355, NMR and Computational Studies of Biomolecules, Antibiotic Biosynthesis: Amino Acid Morphing, Modular Enzymatic Assembly Lines for Antibiotics, 5S RRNA RECOGNITION BY TRANSCRIPTION FACTOR IIIA