Function
Fatty acid synthase beta subunit; part of the fragmented gene cluster that mediates the biosynthesis of dothistromin (DOTH), a polyketide toxin very similar in structure to the aflatoxin precursor, versicolorin B (PubMed:12039746, PubMed:17683963, PubMed:22069571, PubMed:23207690, PubMed:23448391). The first step of the pathway is the conversion of acetate to norsolorinic acid (NOR) and requires the fatty acid synthase subunits hexA and hexB, as well as the polyketide synthase pksA (PubMed:16649078, PubMed:23207690). PksA combines a hexanoyl starter unit and 7 malonyl-CoA extender units to synthesize the precursor NOR (By similarity). The hexanoyl starter unit is provided to the acyl-carrier protein (ACP) domain by the fungal fatty acid synthase hexA/hexB (By similarity). The second step is the conversion of NOR to averantin (AVN) and requires the norsolorinic acid ketoreductase nor1, which catalyzes the dehydration of norsolorinic acid to form (1'S)-averantin (PubMed:23207690). The cytochrome P450 monooxygenase avnA then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN) (PubMed:23207690). The next step is performed by adhA that transforms HAVN to averufin (AVF) (PubMed:23207690). Averufin might then be converted to hydroxyversicolorone by cypX and avfA (PubMed:23207690). Hydroxyversicolorone is further converted versiconal hemiacetal acetate (VHA) by moxY (PubMed:23207690). VHA is then the substrate for the versiconal hemiacetal acetate esterase est1 to yield versiconal (VAL) (PubMed:23207690). Versicolorin B synthase vbsA then converts VAL to versicolorin B (VERB) by closing the bisfuran ring (PubMed:16649078, PubMed:23207690). Then, the activity of the versicolorin B desaturase verB leads to versicolorin A (VERA) (PubMed:23207690). DotB, a predicted chloroperoxidase, may perform epoxidation of the A-ring of VERA (PubMed:23207690). Alternatively, a cytochrome P450, such as cypX or avnA could catalyze this step (PubMed:23207690). It is also possible that another, uncharacterized, cytochrome P450 enzyme is responsible for this step (PubMed:23207690). Opening of the epoxide could potentially be achieved by the epoxide hydrolase epoA (PubMed:23207690). However, epoA seems not to be required for DOTH biosynthesis, but other epoxide hydrolases may have the ability to complement this hydrolysis (PubMed:23207690). Alternatively, opening of the epoxide ring could be achieved non-enzymatically (PubMed:23207690). The next step is the deoxygenation of ring A to yield the 5,8-dihydroxyanthraquinone which is most likely catalyzed by the NADPH dehydrogenase encoded by ver1 (PubMed:23207690). The last stages of DOTH biosynthesis are proposed to involve hydroxylation of the bisfuran (PubMed:23207690). OrdB and norB might have oxidative roles here (PubMed:23207690). An alternative possibility is that cytochrome P450 monoogenases such as avnA and cypX might perform these steps in addition to previously proposed steps (PubMed:23207690).
Sequence
MGSQHQSQHNSALIQAARDGEATLSVAFGGQGPSNLNCFNDLLELNKTYGSTLRPLIHTADATLSELASLPHRSGFHEDEGFETLDWLQDPKQAPSREYLALSPMSFPINTLLSLCNYCVTLRALRLDPGQFRSSLHNVVGHSQGIFAAAAIAKADSWESFLEAAEIALKISFWVGLESHTAAPPSHISAAAVQDCVEHGEGQPSSMLGITGLNRAQVEMLVERVNKSLSDDDRHVCLALANSRDKYTIAGPPHSLRAVCVQIREIRAADGVDQSRILFNKRKQEVDALFLPISAPYHSQYLKQVSNNVLDALDVDLVGSELGIPLLHTQSGQNLQDWKSKSIIKAIVCAVTTDMVEWPDVCQRLGSSYILGFGPGNIGNLIHESTEGTGVRVIQMNDRSPGSRGIGARAELFSEEMPPQALDWKQTFGPRLVLDHRGDVQIQTRMTQLLNAPPVMVAGMTPTTVTWDFVSCVMQAGYHVELAGGGYSSEARFEEALRRLAASIPIYRGITCNLLYANPQTIAWQVAVLRRLIKEGISIEGVTIGAGVPSPDVIKEYIAIGLKHISFKPGSIAAIDEVIEIAQAHPQFPIGLQWTGGRAGGHHSHEDLHLPILKTYARIRRCSNIVLIAGSGFGGGSDTYPYISGDWSKSLSYPPMPFDGILLGSRVMVAKEAHTSPQAKQLIVQTEGVGDNDWHTSFETPTGGVITITSEHGQPIHMLATRGVMLWKEFDKRIFSIKDAAKRLSYIRAHREEIITRLNKDYQKPWFGVNGDGQNVDLDRMTYREVLGRMCQLMSRGDNGWTDPSWLAMVKDFVEIAGERFGCQVDAHATKAPEVRTAFEATLGGSVDETLYPEDVALVLELLRRRGRKPPPFVPALDENFETWCKKDSLWQSEDVDSLVGKDVQRACIIQGPVAVRHSTIHDEPVQDILDNICNFHIESLLQSGETPGVARKQDLGRPNSIKKSVPGVQITTEKTTIRYQVHKTDKLPPEMDTLIEHIVGPAADCWTHHCLKDEWVFRDQARLRNPIRAAFLRQIQPGEVIEVRLSRDGNTQAIALKTALFGKSSLQTVLRIASTDGKSIKVALTPPSFLSDKPLGLQFAYQLSRKSRGSKLVEVTPNRLDAIKGFYAQLWVDSNQDVKEAGLNSEFWGEPTTLLAQDVQNYTAVVSRSTSPQLQAWNPTGSVPVDYCIVLAWTALTKPLTIPALQCDLLNLLHRSVNFKYAANARPLRLGDVTQTVSRITSLTIQPTGKLVEVSAELRRNDETVVTITTEFFIVGQFEDYETQFKSFEEPLFEVRVHSVTRQALLQSRKWLVLDDPSMDLAGLTLAFKLNTHTTFDHEGKVGALQVTGSVSRVESTGFDTRIGKVYFKKDSCNGNPVVDFLNRHGYPRVTRQPLENPGWNEGSTVLMKAPAKSNQYAMASKDTNPLHVCGVFARYAGLPDTVVHGMHTSAIVRRAVEWAVGDSDRSRFKKWQVSFEGMVRPNDRLKIQLQHTAMEHGRMIMKVQAFNDETGDKVIEAEAEVEQPRTGYVFCGQGSQEKGMGMSLYNARPEAKALWDRGDQFLREQYGFSLLSLVRENPTTLTINFGGRRGKRIRDNYLAMTKKTSLKADAKDVCIVQGLTPTSTSHTFSETKGLLFSTQFSQPAIALMEMVEHEHLFAKGVVQPSALFAGHSLGEYAALGACTTFMPFESLLTLIFYRGLKMQNALERDANGRTDYSMMAADPSRVGKAGFDERAFQCLVELVNEETGLLMEIVNHNVRSQQYVCAGHFRALWILGKVCDDLAKHPKIHLLSMQDLKDMVTTHVPAAGKLTNDIVLTRGKATIPLNGIDIPFHSTMLRGEIEHFRRYLLTKVNVPDIKPNELVGKWIPNVVGRPFSLDRSYIEHVQSVTGSEPLQKMLKAMA