{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:49:54Z","timestamp":1792043394571,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2026,9,28]]},"abstract":"<jats:p>\n                    Polyketide synthases (PKS), fatty acid synthases (FAS), and non\u2010ribosomal peptide synthetases (NRPS) span a variety of protein architectures and catalytic modalities. Common to all these biosynthetic modalities is the centrality of a phosphopantetheinylated carrier protein, which shuttles substrate either inter\u2010 or intramolecularly between discrete domains that catalyze enzymatic transformations within the assembly line, resulting in these biosynthetic classes being termed \u201cthiotemplated.\u201d In all thiotemplated biosynthetic assembly lines, transient protein\u2013protein interactions mediated by the carrier protein are essential for chain extension and catalysis. In recent years, synthetic analogs of phosphopantetheine (Ppant), known as \u201ccrypto\u2010ACPs,\u201d have become powerful tools for probing certain protein\u2013protein interactions in thiotemplated systems. These crypto\u2010ACP probes are usually created through a chemoenzymatic process. Most existing crypto\u2010ACP probes are designed around mechanism\u2010based approaches, which are aimed at capturing specific protein interactions within these pathways. To develop a more versatile probe capable of capturing a broader range of transient protein\u2013protein interactions, we designed and synthesized a series of diazirine\u2010based phosphopantetheinylated mimics suitable for photocrosslinking using a commonly employed beta\u2010alanine linkage for synthetic tractability. We then evaluated the efficiency of loading\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    AcpP with these diazirine probes as well as crosslinking with\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    FabD. Examination of both loading and crosslinking revealed that deviations from the structure of the natural substrate (4\u2032\u2010phosphopantetheine) of the phosphopantetheinyl (Ppant) arm of the carrier protein resulted in inefficient loading, leading to poor or no crosslinking. These results highlight the limitations of synthetic and structural modularity in\n                    <jats:italic>crypto<\/jats:italic>\n                    \u2010ACP design and will assist future strategies for interrogating protein\u2013protein interactions of this nature.\n                  <\/jats:p>","DOI":"10.1002\/cbic.202500952","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:11:19Z","timestamp":1790169079000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Photoreactive Pantetheinyl Mimics Reveal Design Limitations for Crypto\u2010Acyl Carrier Proteins"],"prefix":"10.1002","volume":"27","author":[{"given":"Anna\u2010Kay R.","family":"West","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Tennessee  Knoxville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawakalitu 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