A biaryl-linked tripeptide from Planomonospora reveals a widespread class of minimal RiPP gene clusters

Abstract

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Understanding the Mechanism of Action of NAI-112, a Lanthipeptide with Potent Antinociceptive Activity

“…In some cases, the discovery of a new RiPP has been accompanied by establishing the correspondent bioactivity [1,3]. However, because most new RiPPs are being discovered through approaches based on structural novelty, they are mostly orphan of an associated biological function (e.g., [4,5]) unless they have measurable antimicrobial activity.…”

A roadmap for metagenomic enzyme discovery

“… 75 A new class of cytochrome p450 enzymes was recently reported to catalyze biaryl linkages of tripeptides in a BGC containing the smallest synthesized and post-translationally modified peptide (RiPP) precursor-encoding gene (18 bp) reported to date. 76 Engineered p450s have dramatically expanded beyond the limits of naturally occurring biocatalysts to catalyze olefin cyclopropanation, 77 carbon–silicon, 78 and carbon–boron bond formation. 79 Structural analysis of cytochrome p450 monooxygenases has provided insights into the reasons underlying their remarkably wide reaction range including the highly-reactive activated oxygen species generated during the catalytic cycle and unusually dynamic elements of the core protein scaffold.…”

Integrating perspectives in actinomycete research: an ActinoBase review of 2020–21

“…This is the case for our selected paper that describes one novel approach based on phylogenetic relationships and evolutionary divergence within a gene cluster to guide the subsequent experimental rationale [92]. Moreover, the chemical-reverse approach can also be informative, which takes compound elucidation as the starting point to go backwards and attempt to link its production to the responsible BGC [93]. Altogether, these different approaches increase the likelihood of discovering new BGCs to access the chemical uniqueness of their respective products, both crucial to discovering novel SMs.…”