The following text describes a protein:
Function:
Hybrid PKS-NRPS synthetase; part of the gene cluster that produces the acyltetronic acid derivatives carlosic acid, agglomerin F and carlosic acid methyl ether. The PKS domains of caaA condenses two malonyl-CoAs into an acetyl starter unit, and form 1,3-diketohexanyl-ACP with the help of the trans-enoyl reductase caaB. Next, the C domain of caaA forms the ester bond between the acyl chain and L-malic acid (derived from the TCA cycle) and accepted by the A domain instead of an amino acid. Finally, the terminal reductase/Dieckmann cyclization (R/DKC) domain cyclizes the intermediate and releases the product as carlosic acid. Decarboxylation of carlosic acid followed by formation of the exocyclic double bond is likely to be catalyzed by the cytochrome P450 monooxygenase caaC. Thus, decarboxylation and oxidation would be coupled (performed by one enzyme) through concomitant abstraction of the hydrogen at C-4. Finally, sequential oxidations of the terminal C-10 methyl group to form carboxylic acid would be catalyzed by the 2-oxoglutarate-dependent dioxygenase caaD, which is required for the biosynthesis of agglomerin F.
Domain:
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. CaaA contains also a polyketide synthase module (PKS) consisting of several catalytic domains including a ketoacyl synthase domain (KS), an acyl transferase domain (AT), a dehydratase domain (DH), a methyltransferase domain (MT), and a ketoreductase domain (KR). Instead of a thioesterase domain (TE), caaA finishes with a reductase/Dieckmann cyclization (R/DKC) domain for product release. CaaA has the following architecture: KS-AT-DH-CMet-KR-ACP-C-A-T-R/DKC.
Sequence:
MAPHPQPEPIAIVGSSCRFPGGSSSPSRLWQLLSNPQDVSKEIPEDRFELQGFYHPKGAHHGTTNVQRAYTLDEDVRIFDAGFFNISPNEADSMDPQQRLLMEVVYEALESGGHPLEGLRGSDTAVFVGTMSVDYNDILIRDLESTPTYFSTGTSRAILANRISYCFDWHGPSMTIDTACSSSMVALHQSVKALRAGEARVAVAGGTELLLGPEQFVGESKMNLLSPTGRSRMWDADADGYARGDGVAAVILKRLSDAIADGDHIESIIRDTGVNQDGKSTGLTVPSSEAQAALIRSTYARAGLDLSNPDDWPQFFEAHGTGTKVGDPREAAAISGCFGSQPIHGNPLYVGSIKTIIGHTEGTAGLAGVLKASLAIQHGVIPPNMLLNRLNPDVKQYYTNLQIPTSPIQWPVLPAGVPRRASVNSFGFGGTNGHAIIEGYEPKASNFDGEQQQPVAPVTSFVFSATTEESLVALLQSYSNYLKINPTIDLHSLAWTLQSRRSAFAYKTAVAASTIDGLVSRLESKVKQAKSTPPTPAGVRSTPATPHLLGVFTGQGAQWPTMGAHLIQISATVRAKLEQLDHSLATLPEADRPSWRIADQLLAPKGESRLSEAALSQPLCTAVQVVLVDLLRSAGITFDAVVGHSSGEIGAAYAAGFISAADAIRIAYYRGVHAKLAQGQKGQKGAMLAVGTSWEDAQELIDLPAFAGKIRIAAHNSAASLTLSGDADAIAHAKRVFDEEKKFARLLLVDTAYHSHHMLPCSGPYIESLRACQIQVNKDRDSSCTWFSSVRADGKPMVADEELQDVYWSDNMVNTVLFADAVKRAAANESLNLAIEVGPHPALKGPAQQNISDVRPSSPLPYTGLLNRGNSDVEAFSDALGSVWTYLGPGTVDFQSYTRLVTPAAPAPKLLTGLPSYQFSRDRVHWHESRRAKKMRRRGAAFHELLGVPSPDNTDQDLRWTNFLKSSEIPWLDGHKLQGQTVFPAAGYVAMALEAGKWLAGDRSVQVLEVRNLTIDRAITFDDGAGFAVETLVALTGISPMSAAKNNSSSSSQMADFAVYACPNTGSLGLELVSSGQVHIVYGAPSFSVLASTPLDDSNMTSIDCEQFYSTLSGLGYGYNGPFHTLAETKRRLGQASATVATYAYSDDERPLIVHPTMLDVAFQASFLAQTSPGDEQLWSLHVPTSIKCVRINPELSASLPTASVELPLSAVLHEPESISLHSSVDVFTENKRETLLQVEGLIMKPFSPATAADDRPMFSTMEYGVAVPNAGVATGHEHPTDKEVVLAGVCDRVAYYYLRAWEAKAGDEEERFRHLLSTFVGGQHSSMTEAWSSDEEKDIQALISQYPESTDLQLLATLGDSFSTETLAQPLLDECFSRGVGFARASAGLARTVQQISHRYPHAKIVEIGAGRGHTTETVLSAIGDAFSSYTFTDTSDDIFGTVAETFQAHGKKIDYKAFNPAKAPSAQGFTEHSYDVAILPNSIYTSSSLQTALGNIRRLLKPGGYLVASAITHEPVRVQALLAGVSLSSDDPRASVSTWHSALRNAGFSGIDTISAEADRRVWPVSVLTAQAINDRTQLLRKPLSSFKGGFRLHEVVILAGKSWESSRLAEEISDLAGRFCDKVTVLEELPTDDDEISPMATFISLLDLSEPVFEEMSEEKMEGLKCLFELSKNILWVTHNARAGSPYHYASIGFGRSIAYEMPHLMLQFLDLDEVEDVVASSRVITESVVRLAALVEWEDKEMLWSLEPELYVEKGQVLVPRIRPNDEQNARINSLRRPVSEVVDPRQGTVRVVPQAGDGASLVLRKEPWDSSPLAMQIRQSTLHALAVTGESMLFVGIGTKEATGETVIALSSTNASRSVPLVSLPTNIADLDQSAGLLASTANHLLAASILASIPANGHLLLHEPAPDGSLASALASQAAEKNVRVTFSTNSATTGDATWIKLNPWTPEHLLKQQLPAGLTHFMDLASPESQVRKYLPLGCRPISVHDLARAQATNHSPGDDRTALLESLKGAVSRAITATATTASGSTAQTAVFPSQIRDLELPSSPVSIIDWTVEATVPAEVRPLDATRYFSRDRTYLLVGLAGQLGQSICEWMARHGAGTVCLTSRSAKADPEWQAAMQKLGTTVRFDVLDVTKREQVEKLVSELGTTCSPIAGVINGAAVFNDMLFSEMSLEVMERVTQPKIIGTKNLNEVFGTTPLDFFVVLSSLTSVIGNSGQTNYTAANAYMTGLVGERRSRGLTGSSLEIGRVAGIGYMERAGDIAREQLIRFGFMAISETDLHQLLAEAIHAGAPSSALAPVVTTGCRTARDDEEVPVAWFHDPRFSHKVIEAREQGSASEGKKSALPVQEQLAQATSKDEAFKVLKDCFAAKLAMISRLSDDQVGHNIPLVELGIDSLVAVEVRGWFLKELKTDMPVLKVLGGGSVADLWGSVAASPATVSKPAAAPPAPKSEDSSASSAGPSSGSRSPLETPSTPPVGEEAKQVNLSEAAERAAKFQEGKQPDSPAYVKSELVSFAQSRFWFLRLLIEDQTTFNVCFYYRITGNLRVGDLERAVRLVTNRHESLRTCFVADEKEADLAHQKVLRQSVVRLERKKIDRLEELHAEYAAMKTIPFDIASGKTLRLILLTLSPTENYLLFNYHHILMDGVSLQNFLTDLEKAYQRQPLGPPPRQLPDFSRSQRAAFQQGKMNEEVTYWRQQFPDGHHPVLPLLPVAKVNTRAPMKAFNVNQVQYRLSKTLVNQVKERAKAHRSTTFHFYLAVFRAMLFRFTEAKDLTIGIADANRNDSDVMGTIGLLLNLLTLRFQNESTQSFGDCLAESRDKAYEALHHSRVPFDVLLKELNVPRSASYSPFFQAFFDYRQGHQEKQQFGNTELEMVELHPGRTAYDMTLDITDSSDSALILFRTQAGLYNPTATQLLLDTYVHLLETFAENTSLDLGNVSLFSDEQRKRAVDVGRGLDLKSAWPETLPLRIDQIAATNRDRIALKDGHGRILTYAVMINRIEAIAEELQKSGVQEGHRVLVFEDATADWPCSMLAIMRLGAVYVPLDLRNPLPRLADVAANCEPAAILVDNTTAKDIDQVNVTQAKVVNVSHASVKPNKRVPNVSRGDAVAAILYTSGSTGKPKGIVVKHSGLRNEIEGYTTQWGLRAERALQQSAFTFNHSSDQIYTGLTNGGTVYIVPWSKRGDPIEVSQIIQEEGITYTKATPAEYALWLDYGNANLRKATNWRFGFGGGESLTPALLHQLAALGLPHLRFFNSYGPTEISISSTKMEIAYREKQPEGRIPCGYSLPNYAAYILDEQQKPLPVGMPGELWIGGAGVSLGYLNNPELTDYHFYPDPYATTEYLAQGWTRMYRTGDIAHLQADGAMVFHSRVAGDAQVKIRGLRIELGDIESNIVKTSDGALREAVVTLRDGDPPLLVAHVVFAPNHNITDTEAFLDHLLQHLPVPQYMVPVMAIPLDRMPLSNHSKVDRKALKALPLPRRTVSSDAVDVLSETMLQLRRRMGRGPPHGGTRPADCPIDQLLHHRGKLPSRRPPTIPHPTPVQRDGAAGRPPRSQQSQRHGQTDRRKHYSQRNRLEARIRTSTRFDGTLSLHYLRPTSP