Work

Roads to Rome: Role of Multiple Cassettes in Cyanobactin RiPP Biosynthesis

Year: 2018

Type: article

Abstract: Ribosomally synthesized and post-translationally modified peptides (RiPPs) are ubiquitous natural products. Bioactive RiPPs are produced from a precursor peptide, which is modified by enzymes. Usually, a single product is encoded in a precursor peptide. However, in cyanobactins and several other RiPP pathways, a single precursor peptide encodes multiple bioactive products flanking with recognition sequences known as "cassettes". The role of multiple cassettes in one peptide is mysterious, but in general their presence is a marker of biosynthetic plasticity. Here, we show that in cyanobactin biosynthesis the presence of multiple cassettes confers distributive enzyme processing to multiple steps of the pathway, a feature we propose to be a hallmark of multicassette RiPPs. TruD heterocyclase is stochastic and distributive. Although a canonical biosynthetic route is favored with certain substrates, every conceivable biosynthetic route is accepted. Together, these factors afford greater plasticity to the biosynthetic pathway by equalizing the processing of each cassette, enabling access to chemical diversity.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.8b09328

Authors: Wenjia Gu, Debosmita Sardar, Elizabeth Pierce, Eric W. Schmidt

Institution: University of Utah

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funders: University of Utah, National Institute of General Medical Sciences

Awards: G1109581895, G508743164, Directed posttranslational modifications for drug design and discovery, G8093193691