Fatty acid, polyketide, and non-ribosomal peptide biosynthesis are essential components to all forms of life and carrier proteins are central to these pathways. During biosynthesis, intermediates are covalently attached to the carrier protein, which protects the intermediates from the cytosolic environment. The carrier protein only presents the substrate to a partner protein when the two proteins interact thus regulating substrate modification. Substrate sequestration in carrier proteins has been reported in both fatty acid and polyketide systems, only recently we revealed this phenomenon in non-ribosomal peptide systems. One subfamily of non-ribosomal peptide carrier proteins is involved in the biosynthesis of pyrrole units, which are incorporated into downstream pathways to generate important medicinal natural products. An adenylation domain is a necessary carrier protein partner for the generation of the pyrrole units. Interestingly, pyrrole carrier proteins are not compatible with homologous partner proteins illustrating the importance of specific protein-protein interactions. Here we use NMR methods to elucidate the role carrier proteins play in the generation of pyrrole units. The results provide insight on carrier protein sequestration of attached intermediate substrates and protein-protein interaction in pyrrole biosynthesis.

Substrate sequestration and protein-protein interactions in pyrrole biosynthesis

251st National Meeting (2016)

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