title: A Highly Promiscuous ß-Ketoacyl-ACP Synthase (KAS) III-like Protein Is Involved in Pactamycin Biosynthesis.
abstract: β-Ketoacyl-acyl carrier protein (β-Ketoacyl-ACP) synthase (KAS) III catalyzes the first step in fatty acid biosynthesis, involving a Claisen condensation of the acetyl-CoA starter unit with the first extender unit, malonyl-ACP, to form acetoacetyl-ACP. KAS III-like proteins have also been reported to catalyze acyltransferase reactions using coenzyme A esters or discrete ACP-bound substrates. Here, we report the in vivo and in vitro characterizations of a KAS III-like protein (PtmR), which directly transfers a 6-methylsalicylyl moiety from an iterative type I polyketide synthase to an aminocyclopentitol unit in pactamycin biosynthesis. PtmR is highly promiscuous, recognizing a wide array of S-acyl-N-acetylcysteamines as substrates to produce a suite of pactamycin derivatives with diverse alkyl and aromatic features. The results suggest that KAS III-like proteins may be used as versatile tools for modifications of complex natural products.
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University , Corvallis, Oregon 97333, United States.
authors.forename: Mostafa E
authors.initials: ME
authors.lastname: Abugrain
authors.affiliation: Department of Chemistry, Oregon State University , Corvallis, Oregon 97333, United States.
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Brumsted
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University , Corvallis, Oregon 97333, United States.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Osborn
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University , Corvallis, Oregon 97333, United States.
authors.forename: Benjamin
authors.identifier: 0000-0003-2085-0873
authors.initials: B
authors.lastname: Philmus
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University , Corvallis, Oregon 97333, United States.|Department of Chemistry, Oregon State University , Corvallis, Oregon 97333, United States.
authors.forename: Taifo
authors.identifier: 0000-0001-9639-526X
authors.initials: T
authors.lastname: Mahmud
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000378:metabolism*; D002384:Catalysis; D003065:Coenzyme A / Q000378:metabolism; D015394:Molecular Structure; D010142:Pactamycin / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D010142:Pactamycin; C077402:3-ketoacyl-acyl carrier protein synthase III; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D003065:Coenzyme A