Protein: Non-reducing polyketide synthase nvfA (EC 2.3.1.-) (Novofumigatonin biosynthesis cluster protein A) (A0A2I1BSV9)
Organism: Aspergillus novofumigatus (strain IBT 16806)
Function: Non-reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of novofumigatonin, a heavily oxygenated meroterpenoid containing a unique orthoester moiety. The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid (DMOA) by the polyketide synthase nvfA via condensation of one acetyl-CoA starter unit with 3 malonyl-CoA units and 2 methylations. DMOA is then converted to farnesyl-DMOA by the farnesyltransferase nvfB. Epoxydation by FAD-dependent monooxygenase nvfK, followed by a protonation-initiated cyclization catalyzed by the terpene cyclase nvfL leads to the production of asnavolin H. The short chain dehydrogenase nvfC then as a 3-OH dehydrogenase of asnovolin H to yield chemesin D. There are two branches to synthesize asnovolin A from chemesin D. In one branch, chemesin D undergoes Baeyer-Villiger oxidation by nvfH, methylation by nvfJ, and enoyl reduction by the nvfM D enoylreductase that reduces the double bond between C-5'and C-6', to form respectively asnovolin I, asnovolin K, and asnovolin A. In the other branch, the methylation precedes the Baeyer-Villiger oxidation and the enoyl reduction to yield asnovolin A via the asnovolin J intermediate. Asnovolin A is further converted to fumigatonoid A by the Fe(II)/2-oxoglutarate-dependent dioxygenase nvfI that catalyzes an endoperoxidation reaction. The alpha/beta hydrolase nvfD then acts as an epimerase that converts fumigatonoid A to its C-5' epimer, which then undergoes spontaneous or nvfD-catalyzed lactonization. The following step utilizes the ketoreductase nvfG to produce fumigatonoid B. The dioxygenase nvfE further converts fumigatonoid B into fumigatonoid C. Finally the Fe(II)/2-oxoglutarate-dependent dioxygenase nvfF catalyzes two rounds of oxidation to transform fumigatonoid C into the end product, novofumigatonin A.
Interaction partners:
Sequence:
MEPSDTERCDVGILFGPQSSDMDEALSCIRSYVLEQPAVRYLVDLVLELPSLWPEIKNAWPALSQVPGEEQLVALGRFFNGGPFPASDEAMNVITTPVTVIRHIVEFYKVKETMKGFQARDVQGFCVGFLAATAVAASCDETAFRALVSKIIRLAVCIGGLVDLDELAVHRARSMAVRWDGEEDYDRLEQVLAAHPEAYIACVTDANRATLTVPKSLAPQMIQDLANHGLSVREIRLCGRFHHPDHTAAVEQMSRLCERDCRFQLPDASSLSLPLRSNINGEVIRTGQLHTIALQSILCFRSQWLITVTAALASITMTDESIRLVSIGPHQCVPRMAQSKLIRTVTSSPVDGCYEAINGTGAAPVRPIAVTGMACRYPQANSVEELWEMLELGKCAVKPLPNDRLKMVELLREPKGPYWGHYLEEPDMFDHRFFGISAREAATMDPQQRLLLQVAYEAMESAGYCGLRSSQIPRDVGCYVGVGSDDYTDNVGSHHANAYSAPGTLQAFNTGRISHYFGWSGPSVVVDTACSSAAVAIHLACQALRTKDCSVAIAGGVNVMTSPKVTQNLAAASFLSPTGASKAFDADADGYCRGEGAGLVVLRPLEDAISDVDPILAVITGTAVNQGSNCSPITVPVSESQMSLYGKSLAASGIAPEDVTYVEAHGTGTQVGDPIEFDSIRRMFGGRHRSEELYVGSIKDNIGHTETSSGVAGLVKTILMMQKGRIPKQANFSRLNPKIPAPEGDRIVIPKQSTDWKSARRVAMVTNYGAAGSNAAIVLRQHTITTNTGSSWLSDVPVFVAAKSPESLRSYCYKMQAFLRQTAGLLGCTMRDITYNLAIKQNRDLDFLVSFPTPSQDPMTLLSQLESVAAGVTDLQQRPAQAPSVILCFGGQNGNTAHISQDLFAGCHLLQAHLADCEKICQSMGLPSLFPTIFQEEPIHDLVNLHCILFAIQYASAMCWIHSGLQVKRMLGHSFGQLTALCVAGGLTLIDAIRLVSERARLIETSWAGDHGVMLSVDASEAEVRALVNRAGDTVDLACYNGARSYVLAGDEISIQVVEKLADGMRIKRLPNTHAFHSRLVDSIVPGLRKLAQSLKYHPTTIPVEACSEDGSAWTCVTPDQIVAHSRMPVHFDSAVQRAANHVQGPVVWLEAGSASPIVSMVRRVVEESSSSRAHLYQASDLKSPQAQANLAKATSGLWANGIPTSHWTEYDPLAFLPASAPIAEASSEPMGLVQVLEKRPSECLFSVNTKDPLYRTCTQGHAVVEQNLCPASLYLEMVVSAAGCLSSAGLITAMPHLQELSISAPLVLEPDGDVLLRLSQSPAEKTAWTFSLFTQAGQKAPVSHATGRISLHPFDSTSTILSRFRSLDRLMNPSRPDSIASLPSSSGLKGSAVYQAFRRVVNYADYYRGVESVFCVSTEATGRVFVPLSLSRESACDPILIDNFVQVAGVHVNCLADVPEDEVYVCSAVGEAFIGEVFMKRDPAAPQPWRVYSNYDRLSKGQVACDVFVMDQKSGQLAIAILAATFTSVSIRALTRTLAKLNNHQPSMLATNEPSAGHKEVNSILNVVDRPPPTAATVDTNKFPAIQAMLSDLLGVGLDELSPYSSLMAIGVDSLMSTEVLTEIKKRFGVNITSAELGEIPDIQCLVQAIFPGASVAQKQATTSKMPPLSDLAESVFNGPAPPDALMLAQKAYDLFGTTQANTDYSQITKWAGFCESVFPKQMALVTAYVVEAFRALGYPLELLHAGQAVPLIPVLPQHESVRNQLYEVLKFSKLICRKDDGMFRTAEAVPSDTSLLLHEDIIKEYPHHASEHTLLRTTGSRLAECLSGSADPLALLFQNADARRVMEDVYTNAPMFKSATMHLAQYLQDLVILLRSRRDIKILEIGAGTGGTTKYLVSQLAAVPGLRFEYTFTDISTSLVTLAKKKFNGYSCIQYATLNIEQDPPDDLLGQYDIVLSTNCIHATRNIAHSCDNIRKLLRPDGILCLIELTRNLFWFDLVFGLLEGWWLFNDGRNHALATEQFWNESLRQAGYNWVNWSCNDSRESEILRLIVASPTLPHGASQILFRSPLVTEETVKYDEKDGVQLLADIYYPSEVDDAHRRRPIALLIHGGGHVMLSRKDIRSQQIKMLLNSGFLPVSIDYRLCPETSLTEGPMRDVRDALVWTRRTLPRLSLKRPDIRPNGDQVVAVGWSTGGHLAMTLSWTASLCGVRAPEAILSFYCPTDYSDPFWSQPNFPYGRDIAPQMKCTIFGMQ