Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters i...

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" Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria "
Harris, Nicholas Charles Zhang, Wenjun

Document Type	:	Latin Dissertation
Language of Document	:	English
Record Number	:	898295
Doc. No	:	TL38g6g6f0
Main Entry	:	El-Tanani, Mohammed Ahmed
Title & Author	:	Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria\ Harris, Nicholas CharlesZhang, Wenjun
Date	:	2019
student score	:	2019
Abstract	:	Mycobacterium tuberculosis is the leading causative agent of tuberculosis, from which millions die annually. A putative lipopeptide biosynthetic gene cluster has been shown to be essential for the survival of this pathogen in hosts, and homologous gene clusters have also been found in all pathogenic mycobacteria and other species of Actinobacteria. However, the specific functions of the encoded proteins have been elusive. Using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoded biosynthetic enzymes are capable of synthesizing a family of isonitrile lipopeptides (INLPs) through a thio-template mechanism. The biosynthesis features the generation of isonitrile from a single precursor Gly promoted by a thioesterase and a nonheme iron(II)-dependent oxidase homolog and the acylation of both amino groups of Lys by the same isonitrile acyl chain facilitated by a single condensation domain of a nonribosomal peptide synthetase. Additionally, the biosynthesis of this bioactive isonitrile moiety is extraordinary and is distinct from the IsnA family of isonitrile synthases. We herein provide the first structural and biochemical evidence of an alternative mechanism for isonitrile formation.
Added Entry	:	Harris, Nicholas Charles
Added Entry	:	UC Berkeley