ライフサイエンスコーパス: NRPS

1 NRPS/PK synthetase or synthase enzymes are generally act

2 n (C(2)-A(2)-PCP(2)-Cy(1)-A(1)-PCP(1)-Cy(0)) NRPS, and BlmIII is a three domain (A(0)-PCP(0)-Ox) NRPS

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

4 tion of a functional C domain excised from a NRPS should aid efforts at swapping NRPS domains between

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

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

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

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

9 on of recognition determinants varies across NRPS systems.

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

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

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

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

14 scribed here are the first indication for an NRPS subunit that homodimerization can occur and that th

15 Thus VibF is an NRPS with two domains, Cy1 and Cy2, that perform a funct

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

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

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

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

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

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

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

23 for generating chemical diversity within an NRPS assembly line.

24 nstitute the two thiazole-forming NRPS-1 and NRPS-0 modules, respectively.

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

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

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

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

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

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

31 primers for NRPS genes failed to amplify any NRPS genes but (unexpectedly) yielded a band (among seve

32 ng of the potential evolution of Aspergillus NRPS.

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

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

35 eport the production of the BlmIV and BlmIII NRPSs as an excised domain(s), module, or intact subunit

36 racterized by domains characteristic to both NRPS and polyketide synthase (PKS).

37 new insight into the reactions catalyzed by NRPS.

38 rstanding the covalent catalysis executed by NRPS and PKS enzymes.

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

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

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

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

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

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

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

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

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

48 standing of the protein domains that compose NRPS assembly lines is required before these megasynthet

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

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

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

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

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

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

55 condensation (C) domain of the enterobactin NRPS EntF was excised from the multidomain synthetase us

56 scherichia coli enterobactin synthetase EntF NRPS subunit.

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

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

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

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

61 n trans aminoacylation of BlmIII-PCP(0) (for NRPS-0), and (c) reveal that the C-terminus of the BlmIV

62 h in cis aminoacylation of BlmIV-PCP(1) (for NRPS-1) and in trans aminoacylation of BlmIII-PCP(0) (fo

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

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

65 DNA or cDNA, and (iv) degenerate primers for NRPS genes failed to amplify any NRPS genes but (unexpec

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

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

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

69 subunit constitute the two thiazole-forming NRPS-1 and NRPS-0 modules, respectively.

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

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

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

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

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

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

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

77 The holo-NRPS module but not the holo-PKS module was then selecti

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

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

80 tants and by characterizing LnmI as a hybrid NRPS-PKS megasynthetase, the NRPS module of which specif

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

82 f approximately 2.5 megadalton active hybrid NRPS/PKS.

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

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

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

86 bstrate protection and regulation in type II NRPS systems.

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

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

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

90 ons in mediating directional chain growth in NRPS and presents the first systematic exploration of ho

91 and protein-protein interaction mechanism in NRPS assembly line enzymology.

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

93 guillarum plasmid pJM1 that encodes a 78-kDa NRPS protein termed AngM, which is essential in the bios

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

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

96 Many NRPS clusters include a small protein of approximately 8

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

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

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

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

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

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

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

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

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

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

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

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

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

110 important implications for engineering novel NRPS/PKSs.

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

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

113 lts suggest a default role for MT domains of NRPS assembly lines in generating alpha-carbanionic spec

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

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

116 he catalytic order of events and kinetics of NRPS and PKS systems.

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

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

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

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

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

122 r proteins has hindered our understanding of NRPS synthesis.

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

124 btH-like proteins are integral components of NRPSs.

125 in (PCP) and the condensation (C) domains of NRPSs, and curiously, these two domains are not associat

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

127 and intermodular aminoacyl transfer steps of NRPSs.

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

129 nderscore the flexibility and versatility of NRPSs in both structure and mechanism for natural produc

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 Unlike other NRPS systems that in general appear to be monomeric, the

133 nd BlmIII is a three domain (A(0)-PCP(0)-Ox) NRPS.

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

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

136 oited for engineering hybrid PKS-PKS and PKS-NRPS (nonribosomal peptide synthetase) junctions and sug

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

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

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

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

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

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

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

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

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

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

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

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

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

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

151 rate in vitro reconstitution of both the PKS/NRPS interface (EpoA-ACP/B) and the NRPS/PKS interface (

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

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

154 te NH(2)-Tyr-Gly-DGln-Ile-Ser-mPro-Leu/Phe-S-NRPS to yield a linear heptapeptide aldehyde that is sub

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

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

157 esis may impart directionality to sequential NRPS domain interactions.

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

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

160 Using components from siderophore NRPSs that synthesize vibriobactin, enterobactin, yersin

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

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

163 d from a NRPS should aid efforts at swapping NRPS domains between assembly lines.

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

165 eptide synthetases and polyketide synthases (NRPSs and PKSs, respectively), synthesize from simple, p

166 tions in the nonribosomal peptide synthesis (NRPS)/polyketide (PK) synthesis or transport of Ybt.

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

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

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

170 ole-forming nonribosomal peptide synthetase (NRPS) as a probe, we localized a 172-kb DNA region from

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

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

173 domains of nonribosomal peptide synthetase (NRPS) assembly lines found in the Ybt or Pch synthetase

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

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

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

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

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

179 ssembled by nonribosomal peptide synthetase (NRPS) enzymes.

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

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

182 (vph) and non-ribosomal peptide synthetase (NRPS) gene probes amplified from S. vinaceus genomic DNA

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 the ncpA-B nonribosomal peptide synthetase (NRPS) is co-linear in arrangement with respect to the pu

186 sized via a nonribosomal peptide synthetase (NRPS) mechanism.

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

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

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

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

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

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

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 trimodular nonribosomal peptide synthetase (NRPS).

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

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

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

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

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

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

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

209 Nonribosomal peptide synthetases (NRPS), fatty acid synthases (FAS), and polyketide syntha

210 Nonribosomal peptide synthetases (NRPS), fatty acid synthases (FAS), and polyketide sythas

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 embled by non-ribosomal peptide synthetases (NRPSs) and modified by accessory enzymes in the cytoplas

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

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

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

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

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

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

221 (PKSs) and nonribosomal peptide synthetases (NRPSs) are two related families of modular megasynthases

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

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

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

225 mains from nonribosomal peptide synthetases (NRPSs) catalyze the final step in the biosynthesis of di

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

227 Nonribosomal peptide synthetases (NRPSs) make many natural products of clinical importance

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

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

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

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

232 Nonribosomal peptide synthetases (NRPSs) use phosphopantetheine (pPant) bearing carrier pr

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

234 at the two nonribosomal peptide synthetases (NRPSs), BlmIV and BlmIII, are responsible for the biosyn

235 ediates in nonribosomal peptide synthetases (NRPSs), mass spectrometry is used to read out the kineti

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

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

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

239 mes called nonribosomal peptide synthetases (NRPSs).

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

241 ltidomain non-ribosomal peptide synthetases (NRPSs).

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

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

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

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

246 The NRPS shares similarity with the yersiniabactin system fo

247 The NRPS-0 module consists of domains residing on two differ

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

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

250 the PKS/NRPS interface (EpoA-ACP/B) and the NRPS/PKS interface (EpoB/C) in the assembly line for thi

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

252 nfunctional, raising the question of how the NRPS-0 module activates and loads the Cys substrate to i

253 nmI as a hybrid NRPS-PKS megasynthetase, the NRPS module of which specifies for L-Cys and catalyzes t

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

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

260 Disruption of the NRPS lpmC gene completely abolished laspartomycin produc

261 main identified at the C-terminal end of the NRPS NcpB is predicted to catalyze an NAD(P)H-mediated h

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

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

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

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

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

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

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

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

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

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

272 also studied the excised TE domains from the NRPSs which biosynthesize the symmetric cyclic decapepti

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

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

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

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

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

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

279 es PCP interactions and movements crucial to NRPS mechanism.

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

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

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

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

284 esis was obtained from the disruption of two NRPS adenylation domains.

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

286 nsation domain VibH, indicating that the two NRPS enzymes share carrier protein recognition determina

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

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

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

290 at the excised TE domain from the tyrocidine NRPS can be used to generate an array of sizes of cyclic

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

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

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

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

295 ed by circular dichroism to the vibriobactin NRPS VibH, a naturally free-standing C domain.

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

297 When NRPS assembly lines have been probed for comparable form

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

299 a few C-terminal reductases associated with NRPSs have been identified, the ncp reductase is the fir

300 e for VibF and establish that domains within NRPS dimeric modules can act on acyl chains in trans.