{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T07:40:58Z","timestamp":1777794058673,"version":"3.51.4"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T00:00:00Z","timestamp":1547596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Antibiotics can damage the gut microbiome leading to opportunistic infections and the emergence of antibiotic resistance. Microbiome protection via antibiotic inactivation in the gastrointestinal (GI) tract represents a strategy to limit antibiotic exposure of the colonic microbiota. Proof of concept for this approach was achieved with an orally-administered beta-lactamase enzyme, SYN-004 (ribaxamase), that was demonstrated to degrade ceftriaxone excreted into the GI tract and protect the gut microbiome from antibiotic-mediated dysbiosis. Ribaxamase efficiently degrades penicillin and cephalosporin beta-lactam antibiotics, but is not active against carbapenems. To expand this microbiome protection strategy to include all classes of beta-lactams, three distinct carbapenemases were evaluated for manufacturability, antibiotic degradation spectrum, and stability in human intestinal fluid. E. coli production strains were generated for P2A, a novel metallo-enzyme isolated from B. cereus, New Delhi metallo-beta-lactamase (NDM), and Klebsiella pneumoniae carbapenemase (KPC). While all three enzymes effectively inactivated a broad range of antibiotics, including penicillins, most cephalosporins, and carbapenems in vitro, only P2A retained biological activity when incubated with human chyme. As functional stability in the intestinal tract is a key requirement for an orally-delivered enzyme, P2A was chosen as a potential clinical candidate. An enteric formulation of P2A was developed, called SYN-006, that was inert under high acid conditions, with enzyme dissolution occurring at pH &gt; 5.5. SYN-006 has the potential to expand microbiome protection via antibiotic inactivation to include all classes of beta-lactam antibiotics.<\/jats:p>","DOI":"10.3390\/microorganisms7010022","type":"journal-article","created":{"date-parts":[[2019,1,18]],"date-time":"2019-01-18T02:22:23Z","timestamp":1547778143000},"page":"22","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Identification, Characterization, and Formulation of a Novel Carbapenemase Intended to Prevent Antibiotic-Mediated Gut Dysbiosis"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0951-3593","authenticated-orcid":false,"given":"Sheila","family":"Connelly","sequence":"first","affiliation":[{"name":"Synthetic Biologics, Inc., Rockville, MD 20850, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8716-2763","authenticated-orcid":false,"given":"Todd","family":"Parsley","sequence":"additional","affiliation":[{"name":"SynPhaGen, LLC, Rockville, MD 20850, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Ge","sequence":"additional","affiliation":[{"name":"AscentGene, Inc., Gaithersburg, MD 20878, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Kaleko","sequence":"additional","affiliation":[{"name":"Synthetic Biologics, Inc., Rockville, MD 20850, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1126\/science.aad9358","article-title":"Antibiotic use and its consequences for the normal microbiome","volume":"352","author":"Blaser","year":"2016","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4554","DOI":"10.1073\/pnas.1000087107","article-title":"Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation","volume":"108","author":"Dethlefsen","year":"2011","journal-title":"Proc. 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