scholarly journals Molecular Basis for Acyl Carrier Protein-Ketoreductase Interaction in trans-Acyltransferase Polyketide Synthases

2021 ◽  
Author(s):  
Munro Passmore ◽  
Angelo Gallo ◽  
Józef Romuald Lewandowski ◽  
Matthew Jenner
Keyword(s):  
Molecular Basis ◽  
Acyl Carrier Protein ◽  
Polyketide Synthases ◽  
Carrier Protein ◽  
Type I ◽  
Catalytic Domains ◽  
In Trans

The biosynthesis of polyketides by type I modular polyketide synthases (PKS) relies on co-ordinated interactions between acyl carrier protein (ACP) domains and catalytic domains within the megasynthase. Despite the importance...

scholarly journals Modular type I polyketide synthase acyl carrier protein domains share a common N-terminally extended fold

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Luisa Moretto ◽  
Rachel Heylen ◽  
Natalie Holroyd ◽  
Steven Vance ◽  
R. William Broadhurst
Keyword(s):  
Polyketide Synthase ◽  
Acyl Carrier Protein ◽  
Protein Domains ◽  
Carrier Protein ◽  
Type I

Modeling of Human Fatty Acid Synthase and in Silico Docking of Acyl Carrier Protein Domain and Its Partner Catalytic Domains

2018 ◽  
Vol 122 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Matilde F. Viegas ◽  
Rui P. P. Neves ◽  
Maria J. Ramos ◽  
Pedro A. Fernandes
Keyword(s):  
Fatty Acid ◽  
In Silico ◽  
Fatty Acid Synthase ◽  
Acyl Carrier Protein ◽  
Protein Domain ◽  
Carrier Protein ◽  
In Silico Docking ◽  
Catalytic Domains

Solution Structure of an Acyl Carrier Protein Domain from a Fungal Type I Polyketide Synthase,

Biochemistry ◽  
2010 ◽  
Vol 49 (10) ◽  
pp. 2186-2193 ◽  
Author(s):  
Pakorn Wattana-amorn ◽  
Christopher Williams ◽  
Eliza Płoskoń ◽  
Russell J. Cox ◽  
Thomas J. Simpson ◽  
...  
Keyword(s):  
Solution Structure ◽  
Polyketide Synthase ◽  
Acyl Carrier Protein ◽  
Protein Domain ◽  
Carrier Protein ◽  
Type I

The Toxic Dinoflagellate Karenia brevis Encodes Novel Type I-like Polyketide Synthases Containing Discrete Catalytic Domains

Protist ◽  
2008 ◽  
Vol 159 (3) ◽  
pp. 471-482 ◽  
Author(s):  
Emily A. Monroe ◽  
Frances M. Van Dolah
Keyword(s):  
Karenia Brevis ◽  
Polyketide Synthases ◽  
Type I ◽  
Toxic Dinoflagellate ◽  
Catalytic Domains

Ketosynthases in the Initiation and Elongation Modules of Aromatic Polyketide Synthases Have Orthogonal Acyl Carrier Protein Specificity†

Biochemistry ◽  
2003 ◽  
Vol 42 (21) ◽  
pp. 6588-6595 ◽  
Author(s):  
Yi Tang ◽  
Taek Soon Lee ◽  
Seiji Kobayashi ◽  
Chaitan Khosla
Keyword(s):  
Acyl Carrier Protein ◽  
Polyketide Synthases ◽  
Carrier Protein ◽  
Protein Specificity

scholarly journals A Mammalian Type I Fatty Acid Synthase Acyl Carrier Protein Domain Does Not Sequester Acyl Chains

2007 ◽  
Vol 283 (1) ◽  
pp. 518-528 ◽  
Author(s):  
Eliza Ploskoń ◽  
Christopher J. Arthur ◽  
Simon E. Evans ◽  
Christopher Williams ◽  
John Crosby ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Acyl Carrier Protein ◽  
Protein Domain ◽  
Carrier Protein ◽  
Type I ◽  
Acyl Chains

scholarly journals Structural and evolutionary relationships of “AT-less” type I polyketide synthase ketosynthases

2015 ◽  
Vol 112 (41) ◽  
pp. 12693-12698 ◽  
Author(s):  
Jeremy R. Lohman ◽  
Ming Ma ◽  
Jerzy Osipiuk ◽  
Boguslaw Nocek ◽  
Youngchang Kim ◽  
...  
Keyword(s):  
Amino Acid ◽  
Substrate Specificity ◽  
Polyketide Synthase ◽  
Acyl Carrier Protein ◽  
Structural Diversity ◽  
Type I ◽  
Substrate Specificities ◽  
In Trans ◽  
Canonical Type ◽  
Insight Into

Acyltransferase (AT)-less type I polyketide synthases (PKSs) break the type I PKS paradigm. They lack the integrated AT domains within their modules and instead use a discrete AT that acts in trans, whereas a type I PKS module minimally contains AT, acyl carrier protein (ACP), and ketosynthase (KS) domains. Structures of canonical type I PKS KS-AT didomains reveal structured linkers that connect the two domains. AT-less type I PKS KSs have remnants of these linkers, which have been hypothesized to be AT docking domains. Natural products produced by AT-less type I PKSs are very complex because of an increased representation of unique modifying domains. AT-less type I PKS KSs possess substrate specificity and fall into phylogenetic clades that correlate with their substrates, whereas canonical type I PKS KSs are monophyletic. We have solved crystal structures of seven AT-less type I PKS KS domains that represent various sequence clusters, revealing insight into the large structural and subtle amino acid residue differences that lead to unique active site topologies and substrate specificities. One set of structures represents a larger group of KS domains from both canonical and AT-less type I PKSs that accept amino acid-containing substrates. One structure has a partial AT-domain, revealing the structural consequences of a type I PKS KS evolving into an AT-less type I PKS KS. These structures highlight the structural diversity within the AT-less type I PKS KS family, and most important, provide a unique opportunity to study the molecular evolution of substrate specificity within the type I PKSs.

Acyl carrier protein: structure–function relationships in a conserved multifunctional protein family

2007 ◽  
Vol 85 (6) ◽  
pp. 649-662 ◽  
Author(s):  
David M. Byers ◽  
Huansheng Gong
Keyword(s):  
Fatty Acid ◽  
Active Sites ◽  
Fatty Acid Synthase ◽  
Acyl Carrier Protein ◽  
Divalent Cations ◽  
Structural Features ◽  
Carrier Protein ◽  
Type I ◽  
Prosthetic Group

Acyl carrier protein (ACP) is a universal and highly conserved carrier of acyl intermediates during fatty acid synthesis. In yeast and mammals, ACP exists as a separate domain within a large multifunctional fatty acid synthase polyprotein (type I FAS), whereas it is a small monomeric protein in bacteria and plastids (type II FAS). Bacterial ACPs are also acyl donors for synthesis of a variety of products, including endotoxin and acylated homoserine lactones involved in quorum sensing; the distinct and essential nature of these processes in growth and pathogenesis make ACP-dependent enzymes attractive antimicrobial drug targets. Additionally, ACP homologues are key components in the production of secondary metabolites such as polyketides and nonribosomal peptides. Many ACPs exhibit characteristic structural features of natively unfolded proteins in vitro, with a dynamic and flexible conformation dominated by 3 parallel α helices that enclose the thioester-linked acyl group attached to a phosphopantetheine prosthetic group. ACP conformation may also be influenced by divalent cations and interaction with partner enzymes through its “recognition” helix II, properties that are key to its ability to alternately sequester acyl groups and deliver them to the active sites of ACP-dependent enzymes. This review highlights recent progress in defining how the structural features of ACP are related to its multiple carrier roles in fatty acid metabolism.

scholarly journals Bacterial Product Template Domain: An Evolutionary Intermediate between Dehydratase and Aldol Cyclase of Type I Polyketide Synthases

2021 ◽  
Author(s):  
yuanyuan Feng ◽  
Xu Yang ◽  
Huining Ji ◽  
Zixin Deng ◽  
Shuangjun Lin ◽  
...  
Keyword(s):  
Acyl Carrier Protein ◽  
Structural Similarity ◽  
Polyketide Synthases ◽  
Type I ◽  
Tetraacetic Acid ◽  
Bacterial Product ◽  
Aldol Cyclization ◽  
Dimerization Interface ◽  
Acid Lactone

Abstract The product template (PT) domains act as an aldol cyclase to control the regiospecific aldol cyclization of the extremely reactive poly-β-ketone intermediate assembled by an iterative type I polyketide synthases (PKSs). Up to now, only the structure of fungal PksA PT that mediates the first-ring cyclization via C4-C9 aldol cyclization is available. We describe here the structural and computational characterization of a bacteria PT domain that controls C2-C7 cyclization in orsellinic acid (OSA) synthesis. Mutating the catalytic His949 of the PT abolishes production of OSA and results in a tetraacetic acid lactone (TTL) generated by spontaneous O-C cyclization of the acyl carrier protein (ACP)-bound tetraketide intermediate. Crystal structure of the bacterial PT domain closely resembles dehydrase (DH) domains of modular type I PKSs in the overall fold, dimerization interface and catalytic “His-Asp” dyad organization, but is significantly different from PTs of fungal iterative type I PKSs. QM/MM calculation reveals that the catalytic His949 abstracts a proton from C2 and transfers it to C7 carbonyl to mediate the cyclization reaction. According to the structural similarity to DHs and the functional similarity to fungal PTs, we propose that the bacterial PT represents an evolutionary intermediate between the two tailoring domains of type I PKSs.

scholarly journals A universal pocket in Fatty acyl-AMP ligases ensures redirection of fatty acid pool away from Coenzyme A-based activation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Gajanan Shrikant Patil ◽  
Priyadarshan Kinatukara ◽  
Sudipta Mondal ◽  
Sakshi Shambhavi ◽  
Ketan D Patel ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Binding Sites ◽  
Molecular Basis ◽  
Coenzyme A ◽  
Acyl Carrier Protein ◽  
Fatty Acyl ◽  
Carrier Protein ◽  
Binding Pockets ◽  
Fatty Acid Pool ◽  
Do So

Fatty acyl-AMP ligases (FAALs) channelize fatty acids towards biosynthesis of virulent lipids in mycobacteria and other pharmaceutically or ecologically important polyketides and lipopeptides in other microbes. They do so by bypassing the ubiquitous coenzyme A-dependent activation and rely on the acyl carrier protein-tethered 4'-phosphopantetheine (holo-ACP). The molecular basis of how FAALs strictly reject chemically identical and abundant acceptors like coenzyme A (CoA) and accept holo-ACP unlike other members of the ANL superfamily remains elusive. We show FAALs have plugged the promiscuous canonical CoA-binding pockets and utilize highly selective alternative binding sites. These alternative pockets can distinguish adenosine 3', 5'-bisphosphate-containing CoA from holo-ACP and thus FAALs can distinguish between CoA and holo-ACP. These exclusive features helped identify the omnipresence of FAAL-like proteins and their emergence in plants, fungi, and animals with unconventional domain organisations. The universal distribution of FAALs suggests they are parallelly evolved with FACLs for ensuring a CoA-independent activation and redirection of fatty acids towards lipidic metabolites.

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