Function
Involved in the biosynthesis of 12- and 14-membered ring macrolactone antibiotics such as methymycin and neomethymycin, and pikromycin and narbomycin, respectively. Component of the pikromycin PKS which catalyzes the biosynthesis of both precursors 10-deoxymethynolide (12-membered ring macrolactone) and narbonolide (14-membered ring macrolactone). Chain elongation through PikAI, PikAII and PikAIII followed by thioesterase catalyzed termination results in the production of 10-deoxymethynolide, while continued elongation through PikAIV, followed by thioesterase (TE) catalyzed cyclization results in the biosynthesis of the narbonolide.
Sequence
MANNEDKLRDYLKRVTAELQQNTRRLREIEGRTHEPVAIVGMACRLPGGVASPEDLWQLVAGDGDAISEFPQDRGWDVEGLYDPDPDASGRTYCRSGGFLHDAGEFDADFFGISPREALAMDPQQRLSLTTAWEAIESAGIDPTALKGSGLGVFVGGWHTGYTSGQTTAVQSPELEGHLVSGAALGFLSGRIAYVLGTDGPALTVDTACSSSLVALHLAVQALRKGECDMALAGGVTVMPNADLFVQFSRQRGLAADGRSKAFATSADGFGPAEGAGVLLVERLSDARRNGHRILAVVRGSAVNQDGASNGLTAPHGPSQQRVIRRALADARLAPGDVDVVEAHGTGTRLGDPIEAQALIATYGQEKSSEQPLRLGALKSNIGHTQAAAGVAGVIKMVQAMRHGLLPKTLHVDEPSDQIDWSAGTVELLTEAVDWPEKQDGGLRRAAVSSFGISGTNAHVVLEEAPAVEDSPAVEPPAGGGVVPWPVSAKTPAALDAQIGQLAAYADGRTDVDPAVAARALVDSRTAMEHRAVAVGDSREALRDALRMPEGLVRGTSSDVGRVAFVFPGQGTQWAGMGAELLDSSPEFAASMAECETALSRYVDWSLEAVVRQEPGAPTLDRVDVVQPVTFAVMVSLAKVWQHHGITPQAVVGHSQGEIAAAYVAGALTLDDAARVVTLRSKSIAAHLAGKGGMISLALDEAAVLKRLSDFDGLSVAAVNGPTATVVSGDPTQIEELARTCEADGVRARIIPVDYASHSRQVEIIEKELAEVLAGLAPQAPHVPFFSTLEGTWITEPVLDGTYWYRNLRHRVGFAPAVETLAVDGFTHFIEVSAHPVLTMTLPETVTGLGTLRREQGGQERLVTSLAEAWANGLTIDWAPILPTATGHHPELPTYAFQTERFWLQSSAPTSAADDWRYRVEWKPLTASGQADLSGRWIVAVGSEPEAELLGALKAAGAEVDVLEAGADDDREALAARLTALTTGDGFTGVVSLLDDLVPQVAWVQALGDAGIKAPLWSVTQGAVSVGRLDTPADPDRAMLWGLGRVVALEHPERWAGLVDLPAQPDAAALAHLVTALSGATGEDQIAIRTTGLHARRLARAPLHGRRPTRDWQPHGTVLITGGTGALGSHAARWMAHHGAEHLLLVSRSGEQAPGATQLTAELTASGARVTIAACDVADPHAMRTLLDAIPAETPLTAVVHTAGAPGGDPLDVTGPEDIARILGAKTSGAEVLDDLLRGTPLDAFVLYSSNAGVWGSGSQGVYAAANAHLDALAARRRARGETATSVAWGLWAGDGMGRGADDAYWQRRGIRPMSPDRALDELAKALSHDETFVAVADVDWERFAPAFTVSRPSLLLDGVPEARQALAAPVGAPAPGDAAVAPTGQSSALAAITALPEPERRPALLTLVRTHAAAVLGHSSPDRVAPGRAFTELGFDSLTAVQLRNQLSTVVGNRLPATTVFDHPTPAALAAHLHEAYLAPAEPAPTDWEGRVRRALAELPLDRLRDAGVLDTVLRLTGIEPEPGSGGSDGGAADPGAEPEASIDDLDAEALIRMALGPRNT