عنوان

Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria

شماره

TL38g6g6f0

زبان متن نوشتاري يا گفتاري و مانند آن

انگلیسی

عنوان اصلي

Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria

نام عام مواد

[Thesis]

نام نخستين پديدآور

Harris, Nicholas Charles

نام ساير پديدآوران

Zhang, Wenjun

تاریخ نشرو بخش و غیره

2019

کسي که مدرک را اعطا کرده

Zhang, Wenjun

امتياز متن

2019

متن يادداشت

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.

مستند نام اشخاص تاييد نشده

El-Tanani, Mohammed Ahmed

مستند نام اشخاص تاييد نشده

Harris, Nicholas Charles

مستند نام تنالگان تاييد نشده

UC Berkeley

نام الکترونيکي

فرمت انتشار

p

نوع ماده

[Thesis]

کد کاربرگه

276903

سطح دسترسي

a

تكميل شده

Y