{"doi":"10.1016/j.jbc.2021.101434","title":"Malonyl-acyl carrier protein decarboxylase activity promotes fatty acid and cell envelope biosynthesis in Proteobacteria","abstract":"Bacterial fatty acid synthesis in Escherichia coli is initiated by the condensation of an acetyl-CoA with a malonyl-acyl carrier protein (ACP) by the β-ketoacyl-ACP synthase III enzyme, FabH. E. coli Δ fabH knockout strains are viable because of the yiiD gene that allows FabH-independent fatty acid synthesis initiation. However, the molecular function of the yiiD gene product is not known. Here, we show the yiiD gene product is a malonyl-ACP decarboxylase (MadA). MadA has two independently folded domains: an amino-terminal N -acetyl transferase (GNAT) domain (MadA N ) and a carboxy-terminal hot dog dimerization domain (MadA C ) that encodes the malonyl-ACP decarboxylase function. Members of the proteobacterial Mad protein family are either two domain MadA (GNAT-hot dog) or standalone MadB (hot dog) decarboxylases. Using structure-guided, site-directed mutagenesis of MadB from Shewanella oneidensis , we identified Asn45 on a conserved catalytic loop as critical for decarboxylase activity. We also found that MadA, MadA C , or MadB expression all restored normal cell size and growth rates to an E. coli Δ fabH strain, whereas the expression of MadA N did not. Finally, we verified that GlmU, a bifunctional glucosamine-1-phosphate N -acetyl transferase/ N -acetyl-glucosamine-1-phosphate uridylyltransferase that synthesizes the key intermediate UDP-GlcNAc, is an ACP binding protein. Acetyl-ACP is the preferred glucosamine-1-phosphate N -acetyl transferase/ N -acetyl-glucosamine-1-phosphate uridylyltransferase substrate, in addition to being the substrate for the elongation-condensing enzymes FabB and FabF. Thus, we conclude that the Mad family of malonyl-ACP decarboxylases supplies acetyl-ACP to support the initiation of fatty acid, lipopolysaccharide, peptidoglycan, and enterobacterial common antigen biosynthesis in Proteobacteria.","journal":"Journal of Biological Chemistry","year":2021,"id":172969,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":709923,"name":"Christopher D. Radka","orcid":"0000-0002-6037-7710","position":1,"is_corresponding":false},{"id":469111,"name":"Chitra Subramanian","orcid":"0000-0002-1325-0514","position":2,"is_corresponding":false},{"id":598820,"name":"Matthew W. Frank","orcid":"0000-0002-4914-1440","position":3,"is_corresponding":false},{"id":469113,"name":"Charles O. Rock","orcid":"0000-0001-8648-4189","position":4,"is_corresponding":false},{"id":709922,"name":"Sarah Whaley","orcid":"0000-0001-5851-0490","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T23:46:45.768135Z","pmid":"34801557","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}