Protein
D-lysergyl-peptide-synthetase subunit 1
Organism
Epichloe festucae var. lolii
Function
D-lysergyl-peptide-synthetase subunit 1; part of the gene cluster that mediates the biosynthesis of fungal ergot alkaloid ergovaline, the predominant ergopeptine product in E.festucae var. lolii (PubMed:17308187). DmaW catalyzes the first step of ergot alkaloid biosynthesis by condensing dimethylallyl diphosphate (DMAP) and tryptophan to form 4-dimethylallyl-L-tryptophan (By similarity). The second step is catalyzed by the methyltransferase easF that methylates 4-dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-methionine, resulting in the formation of 4-dimethylallyl-L-abrine (By similarity). The catalase easC and the FAD-dependent oxidoreductase easE then transform 4-dimethylallyl-L-abrine to chanoclavine-I which is further oxidized by easD in the presence of NAD(+), resulting in the formation of chanoclavine-I aldehyde (By similarity). Agroclavine dehydrogenase easG then mediates the conversion of chanoclavine-I aldehyde to agroclavine via a non-enzymatic adduct reaction: the substrate is an iminium intermediate that is formed spontaneously from chanoclavine-I aldehyde in the presence of glutathione (By similarity). The presence of easA is not required to complete this reaction (By similarity). Further conversion of agroclavine to paspalic acid is a two-step process involving oxidation of agroclavine to elymoclavine and of elymoclavine to paspalic acid, the second step being performed by the elymoclavine oxidase cloA (By similarity). Paspalic acid is then further converted to D-lysergic acid (By similarity). Ergovaline is assembled from D-lysergic acid and three different amino acids by the D-lysergyl-peptide-synthetase composed of a monomudular (lpsB) and a trimodular (lpsA) nonribosomal peptide synthetase subunit (PubMed:17308187, PubMed:11592979).
Similarity
Belongs to the NRP synthase family.
Sequence
MGSTTVEPVGSTYARPKPLGNLDHRIEQLLGSESVLNESPGHSPNAYGIPYTARNLTLEDVDHCKSLTNKDLSLEFWKSHLQTAKPCILTRLKPGTGSSILSSRQSVKVDLGGVNTTCRNLFDSTGISLMTVFKVAWGMVLSTYTGSDHVCFGYGAARPSMSVDGEQTTIKPLIKMLPCDMLFKGGTTLLGTVHKAESDFICTIPYQSVSIAEIHHGIGTESGALFNTSIIFWPQEDFSDNPITEVLSQKVTETESLTECDIIMHVDSKQQCYLSYWDYFLSDEQANHLAGALNVAMKSIFESPHRPVGQVEMFSYLDQQKLLQWNGQAPIASESCLGDLIGQNCHSRPDSLAVDSWDGFFTYQELDRLSSTLANKLRCAGVGPDVFVTACFDRCKWMPVAMLGIIKAGGAICALDPSYPLGRLTGMCQLLKSTVVLTTANNAQQAEQLALTTIVLGNDLWTGDSYDEQERQAPLSNVCPSNALYAVFTSGSTGKPKGVVVEHRSFSSCALASLKPLDIRPHDRVLHISSYAFDISIFETLATLTAGASVAIPSEKARREDLPGAMRELQATWAFLTPTVARMYQPKDFPSLRTLCLGGEAIHTSDIGLWASKNLVTGYNPAESCPLGISGPADKSAASFLGWSFSSQASWIVDPRDYQKLAPIGAVGELMIEGPAVARGYIHDLTCSHPDSPFVLPPPQWLSRFRASTSQDTRLYRTGDLVQYGSNGSVHFIGRKDLQVKVHGQRVELSEIEFQLHKTLLPLDCKVVVDAVTFTGHTSVIAFITAAEHSDLENEDDAVRSPDVKVITQDFEIRAADAATKLQSILPRHMVPTIYLPVGHIPMSRSGKIDRQKLRSLALSLPRETLYHIGRQPGPGEIVVTDVERRLQLLFAQVLDLSPEKIKADSDFFRLGGDSIYAMKLLALAPQQGPRDLTYEEIFRHPKLRDLAAASSSFSNISLAIPEDLGPAPFSLARDADSLTKIASEQCGVAVGDIEDIYPCTSLQESLIASTAHDQDAYVGVQSFTLNDDIDTTRLKMAWKMTSEGHPILRTRIIQTDSGAPYQAVIRGPLSWSEESSSDDLPPQFQPSIGLGTPLVQLCLTNSRLLVAMHHALYDGWSLPLLLAEVDQAYRQLSVRQLPPFNRYVKHVTETVDSAASFWKAELQDADPVDFPPLPHLNYKPEPRALLTKSITLTAHTNSQHNVTLATELQLAWALTSHTYTNSQDVVFGIISSGRGAPVAGIERMLGPTFASTPLRVPLDPAQDVREALEELQYRLAEQTKYVQIGLQRIRQQGPNAAAACSFQTMLVVEPNQPVKTQSAWFSRHEFLSELTRFSSHSLTLRCKLLAGSVEVTAIYDQLVVPDAQMQRILSQFQHILTQIQGIGSRDTTIGDIDRLSSGDWNELQAWNSTLPPGLELSVHQMVQAKAQMQPEALAIHSWDGDLTYKELEDYAKGLANRLHALGVRPNTFVAIYLQKSLWVVVAQLAVLIAGAAFTTLETSQPINRLRDVCRTVQPTVVLTSDKLRLSGADLEVPAPLLVINQQLLLEEPGSHSRPLENHTIMASDAMYSIATSGTTGKPKVVVIEHQAFLANSKHLIDRWGFTADSRVLQFAGYSFDAMIVEHFITLLAGGCICIPSSFDRDNRLATCIVEMRVNWAMLTSSVIPLFTPAAVPTLQTLVQAGEPMHQGITDCWASHVQLFNAYGPTECSVISTTSNIINPDARNPRNIGFTTGGVCWIVDPENPESPPVPIGAEGELIIEGAILARGYLGDRVRTAAAFTLRPGWLDDFRGSSGDNRIYRTGDIVRYDPDGSISYVRRKDSQVKLRGQRVELLDVEHHLQNCFPGALQVVADIVTVPNTQSSALVALVLATPTSSSSVAIESCSNDDQATTAHGLLLLANNPQFLIDASAAELALQDRVPSYMVPSLFIPTSRFPRDVSGKVNRGEITRSLAALSRQEWDGYVSTNRVAPTSGLERELQKIWARILNIPPDTIGVHDSFFRLGGDSITCMQVAAQCSRTGILITVKDIFKRRTIEKLAAAAVVVQCPESSTTERVNTAEAKFSFYGPGQLEEYMIQIQPQLGEGQVVEDIYPCSPIQRGILMSHARNSGNYEEVIQWKVISRAPVDVCRLRDAWAQVVDRHAVLRTLFLHVCKENYLDQVVLRSHSPMVLVYNEGEEPVNPVSTGCSQPMHHLRVKRSSAGGITVRLHINHALVDGASLFIIRRDLAMAYEGRLASSRASSPYRDYIAYLQNCHSQIQSNEYWQSYMEGTAPCLFPTLKNAGAQDSQQPFEAFTLQLGATADLNQFCENHRLALTSVLHVVWAMVVQRYTAMDEVCFGYMTSGRHVPVAGVQDIVGPLFNMLVARVGLPHDATLLSVMQKYHDNFLISLDHQHQSLAETLHSIGSASGELFNTLVSIFNDQREGEPAHKSSAVTLVGDDIHSRSEYAITLNVLMLADQVHIQLSYHTSWLSDNYARMIAETFRHVLATVLGQPQLRLNEIEMLDEEHRSGLYGRNHAAVPSFDSCIHYTIHQRCLESPESPAICAWDGDFSYRRLDQLSSSLAEELIGHGVGVEMTIPVLLEKTCWTPVAMLAVLKSGASFVLMDASHPLGRLQTICEAINPPVILASPQTRSKAVGLTSHVIEVTNRLLEQEQAEQQQTWPRVVTKGSNAAYVVFTSGSTGKPKGAIVDHSCLATAAGHLPSRMYINSASRVLQFSSHAWDIPVTDVLLTLRVGGCVCIPSDEERIGNLAQVANRMMVNWALLTPTVARLVKPEDFTHLQTLVLAGEAVSSTDLTTWHDKVRLIQGYGPAECSLVSTVSEPLTPSDNPRNIGQPNGCVAWVVHRDNHHLLAPSGAIEELVLEGPIVSRGYINDPERSAAVFVDPPTWLTRLRGGHSPTRLYKTGDLVSAGLDGCLSFVGRKDDQVKIRGQRVELGEVEALASQAFPGSHVVVETVKDLSSTILVAFILQKETAHAQPSSISSLLHPPSPLFRELISAASCSLRETMPSFMIPTVFLPLAHLPKAPTGKTDRKFLRGHVASLSRMELEAYSIVDATGRAPSTPLETRLQELVGRVLHRSPESIPLDEDLFTFGLDSLTAMTLATLVREDGLAISVPTIFQRPRLSELAVVLNQEQQIKQGQFLAPPPNALMASMDELCAQWQLDRSQVVNIAPTTYYQRGSLASHHTNFIALHFSQPLDPIPFRNAVVGLVQKHAILRTAFVPFRETFVQLILRDFDLPVQEIRTDEDDPSVVAESFCREADRVPVSFGTPITQLYMILGRAGDRLSAVLRLQRAQYDGVAVSCMIADLRSAFDEAPSSALPTLEYADYVISRRAHSSPPVFQVWRELLQGSSMTYLVPPTEYIRSTDRSRTELLVTSSCDIPMPDTKGGITMATVIKTAWALCLARQTQSKDVVFAQLVRNRHLAIAGIDRTVGPCINYVPVRASLNLDWTAKEFLHWVQRQHIRTMTCDMADWDDLVIESTSWPRDTELGSAVHYLSAPVASDYTFAGDVPCQFQMYDFKMVHTYPMVTCLPFPSVGDSSLTVLKIILTSAVFGQGVADRLLSLFRDMVHRLTTYPESLVSELLIIR