A0A125R003 · CLA3_CLACD

Function

function

Highly reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of cladosporin, a tricyclic octaketide that acts as an antimalarial agent though inhibition of the Plasmodium falciparum lysyl-tRNA synthetase (PubMed:26783060).
The highly reducing polyketide synthase cla2 is responsible for biosynthesis up to the pentaketide stage, including of the tetrahydropyran (THP) ring, whereas the three subsequent ketide extensions with no reduction are catalyzed by the non-reducing polyketide synthase cla3 (PubMed:26783060).

Biotechnology

Cladosporin has been intensely studied for its antimalarial activity though inhibition of the Plasmodium falciparum lysyl-tRNA synthetase (PubMed:22704625, PubMed:24935905, PubMed:26074468).
Cladosporin has also antifungal activity against dermatophytes, as well as Penicillium and Aspergillus species (PubMed:5169000).

Pathway

Secondary metabolite biosynthesis.

Features

Showing features for active site.

120732004006008001,0001,2001,4001,6001,8002,000
TypeIDPosition(s)Description
Active site538For beta-ketoacyl synthase activity
Active site673For beta-ketoacyl synthase activity
Active site712For beta-ketoacyl synthase activity
Active site987For acyl/malonyl transferase activity
Active site1311Proton acceptor; for dehydratase activity
Active site1500Proton donor; for dehydratase activity
Active site2058For thioesterase activity

GO annotations

AspectTerm
Molecular Function3-oxoacyl-[acyl-carrier-protein] synthase activity
Molecular Functionfatty acid synthase activity
Molecular Functionphosphopantetheine binding
Biological Processfatty acid biosynthetic process
Biological Processsecondary metabolite biosynthetic process

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Non-reducing polyketide synthase cla3
  • EC number
  • Alternative names
    • Cladosporin biosynthesis cluster protein 3

Gene names

    • Name
      cla3

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Dothideomycetes > Dothideomycetidae > Cladosporiales > Cladosporiaceae > Cladosporium

Accessions

  • Primary accession
    A0A125R003

Phenotypes & Variants

PTM/Processing

Features

Showing features for chain, modified residue.

Type
IDPosition(s)Description
ChainPRO_00004370521-2073Non-reducing polyketide synthase cla3
Modified residue1678O-(pantetheine 4'-phosphoryl)serine

Keywords

Family & Domains

Features

Showing features for region, domain, compositional bias.

Type
IDPosition(s)Description
Region9-242N-terminal acylcarrier protein transacylase domain (SAT)
Domain363-793Ketosynthase family 3 (KS3)
Region898-1198Malonyl-CoA:ACP transacylase (MAT) domain
Region1276-1590Product template (PT) domain
Region1279-1420N-terminal hotdog fold
Domain1279-1586PKS/mFAS DH
Region1439-1586C-terminal hotdog fold
Region1594-1637Disordered
Domain1641-1718Carrier
Region1721-1786Disordered
Compositional bias1723-1741Polar residues
Compositional bias1743-1771Basic and acidic residues
Region1805-1950Thioesterase (TE) domain

Domain

Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (By similarity).
The release of the polyketide chain from the non-reducing polyketide synthase is mediated by the thioesterase (TE) domain localized at the C-ter of the protein (By similarity).

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    2,073
  • Mass (Da)
    225,592
  • Last updated
    2016-04-13 v1
  • MD5 Checksum
    9CFF90A167F3E693CB1C7B34B230A8E4
MHNGSESVLLFGDYTEPWIESIDSLCRQAVSEAWLQSFLDDTVTIIKEQKRSIERILQDSLGEFTDLKDLADRHRGRTDEISYVQGLMLFTVRAAYLLQWVKRDPSLLTASHAIGFSGGLANASVLAVAQDFDTLYTACLEGLRIFSRSCRLAIVRSRAIEEGSGSWGWLVVGISSNDLRHALDHFQNSLGIPNSKRSKVGLTGDRWNTVIGPPSTLELVFKQCPAIKSLPKEKLNIHALQHALDLSESDLDYIIGDSALAQSHVNPEFSLWGMAQPKEPWGSWGELLKVVIVKMLSEPLDIVGVVDEFSGRLGSVPQVNICNMAMEGPSSHAAYLLSTMKLSGKTVNFENGFGSEKAQSASSGRIAIVGMSGRGPGCEDLEEFWNVISNAQDQHQEIPKDRFNLEDYLKQGHVTHCQSESMAKHGCFITKPGEFDARFFHISPREALLMDPGHRMFLMSAYEALETAGYSNGHTKATDPQKISIFFAQCNDDWRIASHDVKGCDSYTLPGTARAFGPGRLAFHLGWEGPAYSMDSACASSVSSVHFACMSLKNKDTDMAVVGAANVIGYPHTFISLSQSGVLSRTGNCKPFRDDADGYCRADFSGAIVLKRLEDAIAANDNILGVLAGTGRNQAGNATSITTSDTATQTRLFHKVLRSANVSPEDISYVEMHGTGTPIGDPAEMGAIANVFGNRKGNTPLPLGAVKGNVGHSESSAGMASLLKCLMMLQKDAIPPQAGMPHALNPKFPSLSDINVVIPSKLGDFKKTLNMPRRILLNNFDAAGGNGCLLLEEYVPPTSKELNIDEQDPRSTHVVVLSAKTQASHHANKRNLLDWLKTNRSTRIQDIAYTSTARRVHWPLRYAIAASSTQELTTKLESSIARENSESTNGRKSPIVFTFTGQGSQYAGMGAELYSTCFAFRDTIKLCARICDDHQFPDFIDIITDKDIDISTKSPLQIQLALLALEIGLAAFWKSIGVLPDMVVGHSLGEYAALYVAGVLSLGDVFYVVGRRAMLLLDRCEIGSCSMLALNASVATVQAHLDTQPHLSCAVACINGPKATVVSGPLGEIADLQTLFHGNKIRSKLLPVPFAFHSLQMEPILDEFTILAGIATFMQPKIPVASTLLATVVDKEGIFGTQYLAEQTRQRVDFVGALNAVKSKMDDPIWLEVGPSPVCSGLVQATISPSTTKIMSTLDATGSDWSSIAHCLSGLYQNGVDIDWLGLHAPYEGGLTLQALPSYQWDLKDYWMPYVEPSGVDQTVIANTASGRGTMSSSISTCAQYVITETKTPKPQVNLGAPTADAGFKAFIDGHRLRGVPVCAGAVFIEAAETAARYLLKYLGRNDADTAVLSLQDMALIRPITQKSVQANAELQTTATLDSGSKDTVRITFGESLAAGSSQHLGGCLLSICEAGLESQWEKSSFFIRSRMNDIIANVKGGQGHRIQRDIYYALFADTVEYDNPFRGVKEAYVSQDFEEAAAEVILKADPTGTQFTTSPYWTDSLSQLCGFVVNGNPSRPKDITYMMASLGSYIQMGQIVPGKSYFTYSRISDRAQDLVYCDTFVFDNDRLVAQSTNCVFHRVQNVILERLLGKPASSSVPAQASDPLRSKRSPQEARSLPGEAKTEKPGSTIATTSPVLESGKSEQGMFQALIAAIVKTTGGELSELNDDTELADIGVDSIMAIEIVAHVKDATNQDLPLSFVLEYPTIGNLRCAFDEDVSSEFTDSEVTSGTPNSSESVTSEEELPGPEEHAFKEPKDDSPLARRDMDNSNDRSLDGGVLDDGSPQPRVRISLLQGRPVRGKPKFFLIADGSGSIATYIHLPPAKVKMPIYGVDSPFLHCPSRFTPEAGIPAAAKWIVEALMKAQPEGPFFLGGFSGGAMLSYEVARQLAAFDRKVDSMVLIDMCCPRPAVSSDLKESLWNDDIESFEEIASHVGSNVASNMQQHLRAIFKAVSVYHPPSMTAKERPDRTIIIWAKKGMITRCHDVPEIMERLSARGLTRTIPEGFMEDPSFGAIRWSFVSKGANDLGPNGWQKYIGHEPLCLSVDLDHLEMMEPGQVHIFRGAFEEAFRLIEA

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias1723-1741Polar residues
Compositional bias1743-1771Basic and acidic residues

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
KT037692
EMBL· GenBank· DDBJ
AMB51800.1
EMBL· GenBank· DDBJ
mRNA

Similar Proteins

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