Roads
to Rome: Role of Multiple Cassettes in Cyanobactin
RiPP Biosynthesis
Wenjia Gu
Debosmita Sardar
Elizabeth Pierce
Eric W. Schmidt
10.1021/jacs.8b09328.s001
https://acs.figshare.com/articles/journal_contribution/Roads_to_Rome_Role_of_Multiple_Cassettes_in_Cyanobactin_RiPP_Biosynthesis/7339529
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.
2018-11-02 00:00:00
Cyanobactin RiPP Biosynthesis Ribosomally
plasticity
presence
enzyme
cassette
pathway
cyanobactin
precursor peptide
precursor peptide encodes
canonical biosynthetic route