ライフサイエンスコーパス: NRPS

1 mRNA abundance of the 14 NRPS identified in the A. fumigatus genome was analyzed

2 ides the first genetic characterization of a NRPS assembly line that efficiently activates two anthra

3 ded approach, we uncovered the function of a NRPS-like enzyme with unusual domain architecture, catal

4 d work constitutes the first example where a NRPS-embedded KR domain is employed for assembly of a fu

5 first example of a reductase domain within a NRPS scaffold shown to reduce a PCP-peptidyl thioester t

6 ins and molecules gave rise to modern aaRSs, NRPS, and ribosomal ensembles, first organized around no

7 as well as a second anthranilate-activating NRPS in N. fischeri.

8 o-linkage formation which is catalyzed by an NRPS, SylC.

9 We also discovered an NRPS cluster that generates a seven-residue lipopeptide.

10 eta-amino acid moiety into C-1027 follows an NRPS mechanism whereby biosynthetic intermediates are te

11 Here, we present the first structure of an NRPS aryl carrier protein loaded with its substrate via

12 gly, the results are the first example of an NRPS condensation domain catalyzing a C-O bond (ester) f

13 We present the crystal structure of an NRPS Cy domain, Cy2 of bacillamide synthetase, at a reso

14 The use of an NRPS-like enzyme for reductive choline formation is ener

15 of integral epimerization (E) domains of an NRPS.

16 he biochemical characterization of SgcC5, an NRPS condensation enzyme that catalyzes ester bond forma

17 Pseudomonas aeruginosa utilizes an NRPS cluster to synthesize the siderophore pyoverdine.

18 iety, guided by a docking domain, whereas an NRPS EpoB carrier protein contributes l-cysteine.

19 for generating chemical diversity within an NRPS assembly line.

20 non-ribosomal peptide synthetase (NRPS) and NRPS-polyketide synthase (PKS) hybrid BGCs from Photorha

21 nonribosomal peptide synthetases (NRPSs) and NRPS-like enzymes activate and transform carboxylic acid

22 Nonribosomal peptide synthetases (NRPSs) and NRPS-like enzymes have diverse functions in primary and

23 to probe the functions of individual PKS and NRPS catalytic domains at the cellular metabolic level.

24 through heterologous combinations of PKS and NRPS modules from different sources.

25 connection and compatibility of the PKS and NRPS modules mediated by the acyl carrier protein (ACP),

26 The programming rules of both the PKS and NRPS modules were then examined in vitro.

27 he first successful fusion between a PKS and NRPS that make highly divergent products, and four previ

28 and further revealed cross-talk with another NRPS pathway producing the anticancer fumitremorgins.

29 ng of the potential evolution of Aspergillus NRPS.

30 e iterative catalytic mechanism of bacterial NRPSs is known, it remains unclear how fungal NRPSs crea

31 SyrB2, from the syringomycin E biosynthetic NRPS of Pseudomonas syringae B301D.

32 new insight into the reactions catalyzed by NRPS.

33 roles for secondary metabolites produced by NRPS in Aspergillus physiology, ecology, and fungal path

34 activating adenylation (A) domain of the CDA NRPS enables the incorporation of synthetic 3-methyl glu

35 cs could be more widely used to characterize NRPS-PKS pathways with unprecedented genetic and metabol

36 t correspond to any previously characterized NRPS domain.

37 However, such chimeric NRPS modules are often heavily impaired, impeding effort

38 isolated variants of two different chimeric NRPSs with approximately 10-fold improvements in enzyme

39 Here we show that impaired chimeric NRPSs can be functionally restored by directed evolution

40 ssette interacts with three separate cognate NRPS partners.

41 n for the production of the Escherichia coli NRPS product enterobactin to map the surface of the aryl

42 or this enzyme in terminating the colibactin NRPS-PKS assembly line and incorporating two electrophil

43 adenylation (A) domains, and recent complete NRPS module structures provide support for this hypothes

44 is insufficient to account for the complete NRPS catalytic cycle and that the loaded state of the PC

45 d by nature to decouple R*-domain-containing NRPS from the polyketide synthase (PKS) machinery, expan

46 erferometers or ring resonators, but to date NRPS requires TM-modes, so the TE-modes normally produce

47 metry-based proteomics to selectively detect NRPS and PKS gene clusters in microbial proteomes withou

48 l product diversity by intermixing different NRPS modules to create synthetic peptides.

49 in by the action of RapP/FkbP, a four-domain NRPS that also putatively serves to cyclize the chain af

50 dole side chain of FQF, and the three-domain NRPS Af12050 activates l-Ala as the adenylate, installs

51 The intermediates formed during NRPS catalysis are delivered between enzyme centers by p

52 cal modifications to carrier proteins during NRPS synthesis may impart directionality to sequential N

53 This research establishes that efficient NRPS-catalyzed DKP biosynthesis can occur in vivo throug

54 scherichia coli enterobactin synthetase EntF NRPS subunit.

55 s also the case in the context of the entire NRPS assembly line process.

56 tion domain or on the dynamics of the entire NRPS module.

57 We combined module exchanges, NRPS subunit exchanges, inactivation of the tailoring en

58 proteomics approach to screen for expressed NRPSs or PKSs from bacteria with or without sequenced ge

59 P) bound thioester, there are relatively few NRPSs that have been shown to use a nicotinamide cofacto

60 oteins, by catalytic domains is critical for NRPS and polyketide synthase function.

61 eraction described here provides a model for NRPS, PKS and FAS function in general as T-TE-like di-do

62 cteria, many of the gene clusters coding for NRPSs also code for a member of the MbtH-like protein su

63 r approach may be widely applicable even for NRPSs from genetically challenging hosts.

64 uld be replaced with a domain from a foreign NRPS to create a chimeric assembly line that produces a

65 Those include four NRPS genes (lpmA/orf18, lpmB/orf25, lpmC/orf26 and lpmD/

66 condensation domains identified to date from NRPS assembly lines.

67 entially interesting bioactive products from NRPSs and PKSs, thereby augmenting the contribution of m

68 istic insight into this unique dual-function NRPS domain.

69 the difference between bacterial and fungal NRPS mechanisms and provide a framework for the enzymati

70 hranilate adenylation domain code for fungal NRPS and should facilitate detection and cloning of gene

71 rved strategy for DKP biosynthesis by fungal NRPSs.

72 RPSs is known, it remains unclear how fungal NRPSs create products of desired length.

73 hemical and functional diversities of fungal NRPSs.

74 o classes of siderophore biosynthesis genes: NRPS (non-ribosomal peptide synthase) genes and NIS (NRP

75 he bacterial colibactin pathway, a genotoxic NRPS-PKS hybrid pathway found in certain Escherichia col

76 HHxxxDG motif in the structurally homologous NRPS condensation (C) domain.

77 e organizations, and a total of 1,147 hybrid NRPS/PKS clusters were found.

78 ed metabolites to be synthesized by a hybrid NRPS-pteridine pathway.

79 f approximately 2.5 megadalton active hybrid NRPS/PKS.

80 RPS), polyketide synthases (PKS), and hybrid NRPS/PKS are of particular interest, because they produc

81 In addition to being hybrid NRPS/PKS molecules, they also feature an unusual ureido-

82 of unknown natural products from the hybrid NRPS-PKS zwittermicin A biosynthetic gene cluster.

83 bstrate protection and regulation in type II NRPS systems.

84 One family of type II NRPSs produce pyrrole moieties, which commonly arise fro

85 lans, and A. oryzae for domains conserved in NRPS proteins.

86 for redox-incompetent R* domains embedded in NRPS assembly lines.

87 rase (AANAT) fold, which is unprecedented in NRPS biology.

88 the beta-hydroxylase domain integrated into NRPS AltH, while l-erythro (2S, 3R) beta-OHAsp in delfti

89 Here we show that fungal iterative NRPSs adopt an alternate incorporation strategy.

90 We detected known NRPS systems in members of the genera Bacillus and Strep

91 we present the structures of the full-length NRPS EntF bound to the MLPs from Escherichia coli and Ps

92 Many NRPS clusters include a small protein of approximately 8

93 In many NRPS modules, the C domain is replaced by the heterocycl

94 The pyoverdine cluster contains four modular NRPS enzymes and 10-15 additional proteins that are esse

95 sis of peramine is catalyzed by the 2-module NRPS, PpzA-1, which has a C-terminal reductase (R) domai

96 The single-module NRPS IvoA is essential for fungal pigment biosynthesis.

97 wo adjacent A. fumigatus ORFs, a monomodular NRPS Af12050 and a flavoprotein Af12060, are necessary a

98 ninyl or aminoisobutyryl unit by monomodular NRPS enzymes containing adenylation, thiolation, and con

99 T-C* and A*-T*-C) forms of these monomodular NRPS enzymes and by expression, purification, and assay

100 During synthesis, the multidomain NRPSs act as an assembly line, passing the growing produ

101 oading reductase (R) domain of mycobacterial NRPSs performs two consecutive [2 + 2]e(-) reductions to

102 ing oxygenases for maturation of the nascent NRPS lipohexapeptidolactam product.

103 tional Cy domain by excision from its native NRPS module, and examine both its protein-protein intera

104 n-ribosomal peptide synthase) genes and NIS (NRPS Independent Siderophore) genes.

105 , the predicted product of the NocA and NocB NRPSs is L-pHPG-L-Arg-D-pHPG-L-Ser-L-pHPG, a pentapeptid

106 t albopeptide originates from a noncanonical NRPS pathway featuring dehydration processes and catalys

107 clusters that encoded modular and nonmodular NRPS enzymes organized in a gradient.

108 e finding of common occurrence of nonmodular NRPS differs substantially from the current classificati

109 important implications for engineering novel NRPS/PKSs.

110 tempting combinatorial biosynthesis of novel NRPS.

111 Modular Linkers (IMLs) impact the ability of NRPS modules to communicate during the synthesis of NRPs

112 structures highlight the dynamic behavior of NRPS modules, including the module core formed by the ad

113 Our results are discussed in the context of NRPS domain interactions.

114 l facilitate rational genetic engineering of NRPS to generate unnaturally methylated NRPs.

115 nce analysis indicates that the evolution of NRPS machineries was driven by a combination of common d

116 n and presents a remarkably clean example of NRPS evolution through recombinant exchange of functiona

117 or wafer bonding used in the fabrication of NRPS devices.

118 The mechanism of NRPS catalysis is based around sequential catalytic doma

119 Here, we report the widespread occurrence of NRPS and PKS genetic machinery across the three domains

120 The sequence and organization of NRPS genes support incorporation of the unusual monomer

121 We also present the first quantification of NRPS CP backbone dynamics.

122 omain signatures", or functional readouts of NRPS-PKS domain contributions to the pathway-dependent m

123 eukaryotic example of an alternative type of NRPS condensation domain; they also illustrate how the c

124 r proteins has hindered our understanding of NRPS synthesis.

125 The modular architecture of NRPSs suggests that a domain responsible for activating

126 btH-like proteins are integral components of NRPSs.

127 groundwork for the rational reengineering of NRPSs by swapping domains handling different substrates

128 and intermodular aminoacyl transfer steps of NRPSs.

129 h many structural and biochemical studies of NRPSs exist, few studies have focused on the energetics

130 1 [one PKS (N-terminus-KS-AT-MT1-KR-ACP) one NRPS module (Cy3-MT2-PCP3-TE-C-terminus)], was used as a

131 N and pksJ genes that are found on an orphan NRPS/PKS hybrid cluster from Bacillus subtilis.

132 method for the fluorescent profiling of PKS, NRPS, and FAS multidomain modular synthases in their who

133 with a variety of purified recombinant PKS, NRPS, and FAS enzymes in vitro, we apply this duel label

134 the successful engineering of hr-PKS and PKS-NRPS products in fungi.

135 d by a series of promiscuous intermodule PKS-NRPS docking motifs possessing identical amino acid sequ

136 No such mixed iterative PKS-NRPS enzymes have been characterized in bacteria.

137 In vitro analysis of iterative PKS-NRPS has been hampered by the difficulties associated wi

138 The widely found fungal iterative PKS-NRPS hybrid megasynthetases are highly programmed biosyn

139 the modular nature of the components of PKS-NRPS hybrid systems.

140 ynthase-nonribosomal peptide synthetase (PKS-NRPS) that generates cyclo-acetoacetyl-L-tryptophan (cAA

141 ynthase-nonribosomal peptide synthetase (PKS-NRPS) that makes and releases cyclo-acetoacetyl-L-trypto

142 ynthase-nonribosomal peptide synthetase (PKS-NRPS), although two separate hexaketide chains are requi

143 ynthase nonribosomal peptide synthetase (PKS-NRPS), which resembles iterative enzymes known in fungi.

144 hat in Streptomyces transformed with the PKS-NRPS alone.

145 hetic gene cluster of the macyranones as PKS/NRPS hybrid.

146 rom a unique combinatorial non-collinear PKS/NRPS system encoded by a 90 kb gene cluster in which an

147 time insights into the intriguing hybrid PKS/NRPS machinery required for microsclerodermin formation.

148 rst adenylation domain of PksJ (a hybrid PKS/NRPS) and installation on the pantetheinyl arm of the ad

149 Hybrid type I PKS/NRPS biosynthetic pathways typically proceed in a collin

150 l peptide synthetases (NRPSs), and mixed PKS/NRPS systems, contain functional domains with similar fu

151 e group on the isoprene of cyclomarin C post-NRPS assembly.

152 by reverse prenylation and a cascade of post-NRPS reactions culminates in an intramolecular [4+2] het

153 at is shared with many siderophore-producing NRPS clusters.

154 4 IMLs from both well annotated and putative NRPS biosynthetic gene clusters from 39 232 bacterial ge

155 tethered to a thiolation (T) domain on same NRPS module (in cis), or does it methylate this residue

156 is elongated to alpha-KIC-Gly by the second NRPS module in PksJ as demonstrated by mass spectrometri

157 Using MbtH-like proteins from three separate NRPS systems, we show that these proteins copurify with

158 esis may impart directionality to sequential NRPS domain interactions.

159 SOI isolators use nonreciprocal phase shift (NRPS) in interferometers or ring resonators, but to date

160 We identified related siderophore NRPS gene clusters that encoded modular and nonmodular N

161 highlights that allelic variants of a single NRPS can result in a surprising level of secondary metab

162 The single NRPS module of the epothilone assembly line, EpoB, is a

163 y of selection-based approaches for studying NRPS biosynthesis.

164 omal peptide synthetase-polyketide synthase (NRPS-PKS) system of the trans-acyl transferase (AT) type

165 tides (NRPs) are produced by NRP synthetase (NRPS) enzymes that function as molecular assembly lines.

166 ly elusive non-ribosomal peptide synthetase (NRPS) and NRPS-polyketide synthase (PKS) hybrid BGCs fro

167 on modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzyme complexes by

168 e with both nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) modules acting along

169 o-templated nonribosomal peptide synthetase (NRPS) assembly line protein PacH.

170 ound to the nonribosomal peptide synthetase (NRPS) assembly line.

171 to encode a nonribosomal peptide synthetase (NRPS) containing two domains, peptidyl carrier protein a

172 the encoded nonribosomal peptide synthetase (NRPS) domains and modules.

173 -activating nonribosomal peptide synthetase (NRPS) domains through bioinformatics approaches.

174 atalyzed by nonribosomal peptide synthetase (NRPS) domains.

175 thase (PKS)-nonribosomal peptide synthetase (NRPS) enzymes EpoA-F.

176 of several nonribosomal peptide synthetase (NRPS) enzymes is used to combine the building blocks int

177 ssembled by nonribosomal peptide synthetase (NRPS) enzymes.

178 m the MalG non-ribosomal peptide synthetase (NRPS) followed by reverse prenylation and a cascade of p

179 xample of a nonribosomal peptide synthetase (NRPS) from a higher eukaryote and contains a C-terminal

180 contains a nonribosomal peptide synthetase (NRPS) gene cluster (aebA-F) resembling that for enteroba

181 a putative nonribosomal peptide synthetase (NRPS) gene cluster (nan).

182 cryptic has nonribosomal peptide synthetase (NRPS) gene cluster in the human pathogen Aspergillus fum

183 thase (PKS)-nonribosomal peptide synthetase (NRPS) hybrid involving proteins EpoA-F.

184 ring of the nonribosomal peptide synthetase (NRPS) in the daptomycin biosynthetic pathway was exploit

185 s a unique non-ribosomal peptide synthetase (NRPS) module comprised of condensation-adenylation-ketor

186 stand-alone nonribosomal peptide synthetase (NRPS) module, and four flavin-dependent oxidoreductases.

187 dissociated nonribosomal peptide synthetase (NRPS) modules and a variety of tailoring enzymes.

188 ries of six nonribosomal peptide synthetase (NRPS) modules distributed over three proteins and a vari

189 rminus of a nonribosomal peptide synthetase (NRPS) or as stand-alone enzymes (TbetaH(Asp))-and each d

190 rived from non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS).

191 e (PKS) and nonribosomal peptide synthetase (NRPS) pathways.

192 two-module non-ribosomal peptide synthetase (NRPS) peramine synthetase (PerA), which is encoded by th

193 acteria use nonribosomal peptide synthetase (NRPS) proteins to produce peptide antibiotics and sidero

194 a 7-module nonribosomal peptide synthetase (NRPS) responsible for assembly of the full-length cyclom

195 of a novel non-ribosomal peptide synthetase (NRPS) system carried by a streptococcal integrative conj

196 thase (PKS)/nonribosomal peptide synthetase (NRPS) systems in streptomycetes.

197 ngle module nonribosomal peptide synthetase (NRPS) to synthesize polyketides conjugated to amino acid

198 ase (PKS), non-ribosomal peptide synthetase (NRPS), and shikimate pathway components, was identified

199 LNM hybrid nonribosomal peptide synthetase (NRPS)-acyltransferase (AT)-less type I polyketide syntha

200 enicol in a nonribosomal peptide synthetase (NRPS)-based pathway to yield the nitroaryl group of the

201 mplated yet nonribosomal peptide synthetase (NRPS)-independent biosynthetic gene clusters across dive

202 Fub1) and a nonribosomal peptide synthetase (NRPS)-like carboxylic acid reductase (Fub8) in making an

203 trimodular nonribosomal peptide synthetase (NRPS).

204 by a hybrid nonribosomal peptide synthetase (NRPS)/polyketide synthase (PKS) megasynthase followed by

205 nonical nonribosomal polypeptide synthetase (NRPS) or polyketide synthase (PKS) domains.

206 nd ancient non-ribosomal protein synthetase (NRPS) modules gave rise to primordial protein synthesis

207 Non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) produce numerous se

208 Type II nonribosomal peptide synthetases (NRPS) generate exotic amino acid derivatives that, combi

209 sembled by nonribosomal peptide synthetases (NRPS) using the conformationally restricted beta-amino a

210 omains of non-ribosomal peptide synthetases (NRPS), and firefly luciferase, perform two half-reaction

211 Nonribosomal peptide synthetases (NRPS), polyketide synthases (PKS), and hybrid NRPS/PKS a

212 cies, the non-ribosomal peptide synthetases (NRPS).

213 ication in nonribosomal peptide synthetases (NRPSs) and lay the groundwork for the rational reenginee

214 gle-module nonribosomal peptide synthetases (NRPSs) and NRPS-like enzymes activate and transform carb

215 Nonribosomal peptide synthetases (NRPSs) and NRPS-like enzymes have diverse functions in p

216 Nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) are large enzymes

217 hesized by nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs).

218 duction of nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs).

219 Nonribosomal peptide synthetases (NRPSs) and polyketide synthases are large, multidomain e

220 Nonribosomal peptide synthetases (NRPSs) are a family of multidomain, multimodule enzymes

221 Nonribosomal peptide synthetases (NRPSs) are microbial enzymes that produce a wealth of im

222 Non-ribosomal peptide synthetases (NRPSs) are modular enzymatic machines that catalyze the

223 The nonribosomal peptide synthetases (NRPSs) are one of the most promising resources for the p

224 Nonribosomal peptide synthetases (NRPSs) assemble a large group of structurally and functi

225 osomes and nonribosomal peptide synthetases (NRPSs) carry out instructed peptide synthesis through a

226 Nonribosomal peptide synthetases (NRPSs) catalyze the biosynthesis of many biologically ac

227 (PKSs) and nonribosomal peptide synthetases (NRPSs) comprise giant multidomain enzymes responsible fo

228 Nonribosomal peptide synthetases (NRPSs) generate the core peptide scaffolds of many natur

229 rived from nonribosomal peptide synthetases (NRPSs) into 2,5-diketopiperazines (DKPs) is a crucial st

230 ins of the nonribosomal peptide synthetases (NRPSs) or polyketide synthases (PKSs) found in the biosy

231 Nonribosomal peptide synthetases (NRPSs) produce a wide variety of peptide natural product

232 thases and nonribosomal peptide synthetases (NRPSs) produce complex lipidic metabolites by using a th

233 sembled by nonribosomal peptide synthetases (NRPSs) that are known to display various modes of action

234 number of nonribosomal peptide synthetases (NRPSs) that release their peptide products by hydrolytic

235 Nonribosomal peptide synthetases (NRPSs) underlie the biosynthesis of many natural product

236 es (PKSs), nonribosomal peptide synthetases (NRPSs), and mixed PKS/NRPS systems, contain functional d

237 codes two non-ribosomal peptide synthetases (NRPSs), NocA and NocB, predicted to encode five modules

238 id ligase, nonribosomal peptide synthetases (NRPSs), regulators, transporters, and tailoring enzymes.

239 cursors by nonribosomal peptide synthetases (NRPSs), which are organized into modules.

240 nes called nonribosomal peptide synthetases (NRPSs).

241 nate from non-ribosomal peptide synthetases (NRPSs).

242 mes called nonribosomal peptide synthetases (NRPSs).

243 oducts by non-ribosomal peptide synthetases (NRPSs).

244 ltidomain non-ribosomal peptide synthetases (NRPSs).

245 The PCP1 domain of the N-terminal NRPS module of HMWP2 was swapped with either PCP2 or PCP

246 peptide tailoring reactions on the terminal NRPS module in GPA biosynthesis.

247 The NRPS module in CpaS has a predicted four-domain organiza

248 The NRPS shares similarity with the yersiniabactin system fo

249 ockout mutant, DeltaaebG V. harveyi, and the NRPS knockout mutant, DeltaaebF V. harveyi, do not produ

250 The key interaction between the PKS and the NRPS was dissected and reconstituted in trans by using s

251 sed to position the beta-hydroxylase and the NRPS-bound amino acid prior to hydroxylation.

252 The gene (aba1) encoding the NRPS complex responsible for the synthesis of the cyclic

253 sation (C) and thiolation (T) domains in the NRPS GliP.

254 expressed with NRPS proteins that modify the NRPS peptide products, ensure the availability of substr

255 We named the NRPS product 'equibactin' and genes of this locus eqbA-N

256 A higher frequency of the NRPS and PKS gene clusters was detected from bacteria co

257 Here we show that soluble forms of the NRPS components MbtB, MbtE, and MbtF are obtained when t

258 usly undescribed, noncanonical member of the NRPS condensation domain superfamily is identified, name

259 d to switch the substrate specificity of the NRPS enzyme GrsA-PheA are then compared against the resu

260 sertion of the Pnpt-promotor in front of the NRPS gene.

261 Disruption of the NRPS lpmC gene completely abolished laspartomycin produc

262 Protection of the NRPS peptide products from proteolysis is critical to th

263 In this process the terminal module of the NRPS plays a crucial role as it contains a unique recrui

264 r play a role in the import or export of the NRPS product.

265 The catalytic domains of the NRPS proteins are usually linked in large multidomain pr

266 multiple modules in the DptBC subunit of the NRPS to modify the daptomycin cyclic peptide core.

267 for reductive release and cyclization of the NRPS-tethered dipeptidyl-thioester intermediate.

268 Many copies of the NRPS/PKS assemble into a single organelle-like membrane-

269 Deletions of ORF3488, the NRPS module, and ORF3489, a phosphopantothenoylcysteine

270 ar enzymes Af12050 and TqaB to show that the NRPS enzymes control the stereochemical outcome.

271 We demonstrated that the NRPS NanA incorporates anthranilic acid (Ant) and l-kynu

272 y and that the precursor is not bound to the NRPS during this step.

273 nally, we incubated the polyene-PKS with the NRPS module in the presence of ornithine and adenosine t

274 on/dissociation of the P450 enzymes with the NRPS, followed by specific recognition of the peptide cy

275 derstanding of the possible functions of the NRPSs' peptide products.

276 e show that these proteins copurify with the NRPSs and influence amino acid activation.

277 llow diverse laboratories to spearhead their NRPS-PKS projects with benchtop mass spectrometers.

278 The majority of these NRPS and PKS gene clusters have unknown end products hig

279 Bioinformatic analysis indicates this NRPS-like glycine betaine reductase is highly conserved

280 theinyl arm of the thiolation domain of this NRPS protein.

281 ous expression system for PhsA, one of three NRPS proteins in PTT biosynthesis.

282 es PCP interactions and movements crucial to NRPS mechanism.

283 viously identified is part of the trimodular NRPS Af12080, which we predict is responsible for FQF fo

284 an R domain from Mycobacterium tuberculosis NRPS provides strong support to this mechanistic model a

285 trated by identifying the substrates for two NRPS modules from the pksN and pksJ genes that are found

286 nthetase containing two subunits, HMWP2 [two NRPS modules (N-terminus-ArCP-Cy1-A-PCP1 and Cy2-PCP2-C-

287 eated two active fusion proteins: one or two NRPS modules fused to the TE domain.

288 lation by wild-type AMAT tridomains from two NRPSs involved in biosynthesis of anticancer depsipeptid

289 Gene deletions confirmed that two NRPSs, PacP and PacO, are required for the biosynthesis

290 D-alanine moiety, does not encode a typical NRPS initiation module with the expected A-PCP-E domains

291 For a typical NRPS initiation module, an adenylation (A) domain activa

292 then revealed that a previously unidentified NRPS-PKS gene cluster from Flavobacterium was essential

293 utilized to identify orthologous and unique NRPS among the Aspergillus species examined, as well as

294 rgillus species contain conserved and unique NRPS genes with a complex evolutionary history.

295 These findings unveil an unprecedented NRPS initiation module structure that is characterized b

296 Here we use NRPS adenylation (AD) domain sequencing to guide the ide

297 ly, a 2-aminoisobutyric acid (AIB)-utilizing NRPS module has been identified and reconstituted in vit

298 Verified NRPSs of other fungal DKPs terminate with similar CT dom

299 CPs in holo and substrate-loaded forms visit NRPS catalytic domains in a series of transient interact

300 en, additional proteins are coexpressed with NRPS proteins that modify the NRPS peptide products, ens