Dataset Information

Mapping the biosynthetic pathway of a hybrid polyketide-nonribosomal peptide in a metazoan

ABSTRACT: Polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) hybrid systems typically use complex protein-protein interactions to facilitate direct transfer of intermediates between these multimodular megaenzymes. In the canal-associated neurons (CANs) of Caenorhabditis elegans, PKS-1 and NRPS-1 produce the nemamides, the only known hybrid polyketide-nonribosomal peptides biosynthesized by animals, through a poorly understood mechanism. Here, we use genome editing and mass spectrometry to map the roles of individual PKS-1 and NRPS-1 enzymatic domains in nemamide biosynthesis. Furthermore, we show that nemamide biosynthesis requires at least five additional enzymes expressed in the CANs that are encoded by genes distributed across the worm genome. We identify the roles of these enzymes and discover a mechanism for trafficking intermediates between a PKS and an NRPS. Specifically, the enzyme PKAL-1 activates an advanced polyketide intermediate as an adenylate and directly loads it onto a carrier protein in NRPS-1. This trafficking mechanism provides a means by which a PKS-NRPS system can expand its biosynthetic potential and is likely important for the regulation of nemamide biosynthesis.

INSTRUMENT(S): Liquid Chromatography MS -

SUBMITTER: Likui Feng

PROVIDER: MTBLS2313 | MetaboLights | 2021-06-22

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS2313	Other
	FILES	Other
	a_MTBLS2313_LC-MS___metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS2313_LC-MS___metabolite_profiling_v2_maf.tsv	Tabular

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Publications

Mapping the biosynthetic pathway of a hybrid polyketide-nonribosomal peptide in a metazoan.

Feng Likui L Gordon Matthew T MT Liu Ying Y Basso Kari B KB Butcher Rebecca A RA

Nature communications 20210813 1

Polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) hybrid systems typically use complex protein-protein interactions to facilitate direct transfer of intermediates between these multimodular megaenzymes. In the canal-associated neurons (CANs) of Caenorhabditis elegans, PKS-1 and NRPS-1 produce the nemamides, the only known hybrid polyketide-nonribosomal peptides biosynthesized by animals, through a poorly understood mechanism. Here, we use genome editing and mass spectrometry t ...[more]

PMID: 34389721

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