Abstract
Leinamycin (LNM) is biosynthesized by a hybrid nonribosomal peptide synthetase (NRPS)-acyltransferase (AT)-less type I polyketide synthase (PKS). Characterization of LnmI revealed ketosynthase (KS)-acyl carrier protein (ACP)-KS domains at the NRPS-PKS interface. Inactivation of the KS domain or ACP domain in vivo abolished LNM production, and the ACP domain can be phosphopantetheinylated in vitro. The LnmI KS-ACP-KS architecture represents a new mechanism for functional crosstalk between NRPS and AT-less type I PKS in the biosynthesis of hybrid peptide-polyketide natural products.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Acyl Carrier Protein / chemistry
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Acyl Carrier Protein / metabolism*
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Lactams / chemistry
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Lactams / metabolism*
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Macrolides / chemistry
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Macrolides / metabolism*
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Molecular Conformation
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Peptide Synthases / chemistry
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Peptide Synthases / metabolism*
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Polyketide Synthases / chemistry
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Polyketide Synthases / metabolism*
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Protein Domains
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Thiazoles / chemistry
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Thiazoles / metabolism*
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Thiones / chemistry
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Thiones / metabolism*
Substances
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Acyl Carrier Protein
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Lactams
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Macrolides
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Thiazoles
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Thiones
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leinamycin
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Polyketide Synthases
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Peptide Synthases
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non-ribosomal peptide synthase