Masked cerulenin enables a dual-site selective protein crosslink

Jiang, Ziran; Chen, Aochiu; Chen, Jeffrey; Sekhon, Arman; Louie, Gordon V.; Noel, Joseph P.; La Clair, James J.; Burkart, Michael D.

doi:10.1039/d3sc02864j

Cited by 1 publication

(1 citation statement)

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“…Alternatively, inhibitors targeting the pks machinery, such as small molecules or peptides mimicking pre-colibactin that inhibit colibactin-activating peptidase ClbP (Figure 3), may be used to inhibit colibactin synthesis [119,131,132]. These peptides can be designed to target specific regions of the pks involved in catalysis, substrate binding, or protein-protein interactions, thereby disrupting pks function [133].…”

Section: Inhibiting Pks Biosynthesismentioning

confidence: 99%

Contribution of pks+ Escherichia coli (E. coli) to Colon Carcinogenesis

Sadeghi,

Mestivier,

Sobhani

2024

Microorganisms

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Colorectal cancer (CRC) stands as a significant global health concern, ranking second in mortality and third in frequency among cancers worldwide. While only a small fraction of CRC cases can be attributed to inherited genetic mutations, the majority arise sporadically due to somatic mutations. Emerging evidence reveals gut microbiota dysbiosis to be a contributing factor, wherein polyketide synthase-positive Escherichia coli (pks+ E. coli) plays a pivotal role in CRC pathogenesis. pks+ bacteria produce colibactin, a genotoxic protein that causes deleterious effects on DNA within host colonocytes. In this review, we examine the role of the gut microbiota in colon carcinogenesis, elucidating how colibactin-producer bacteria induce DNA damage, promote genomic instability, disrupt the gut epithelial barrier, induce mucosal inflammation, modulate host immune responses, and influence cell cycle dynamics. Collectively, these actions foster a microenvironment conducive to tumor initiation and progression. Understanding the mechanisms underlying pks+ bacteria-mediated CRC development may pave the way for mass screening, early detection of tumors, and therapeutic strategies such as microbiota modulation, bacteria-targeted therapy, checkpoint inhibition of colibactin production and immunomodulatory pathways.

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Section: Inhibiting Pks Biosynthesismentioning

confidence: 99%