J5JV76 · BSLS_BEAB2

Function

function

Bassianolide nonribosomal synthetase that mediates the biosynthesis of bassianolide (BSL), a non-ribosomal cyclodepsipeptide that shows insecticidal and cancer cell antiproliferative activity (PubMed:19285149, PubMed:23608474, PubMed:23727842, PubMed:29163920, PubMed:31388353, PubMed:31471217).
BSLS first catalyzes the iterative synthesis of an enzyme-bound dipeptidol monomer intermediate from D-2-hydroxyisovalerate and L-leucine before performing the condensation and cyclization of 4 dipeptidol monomers to yield the cyclic tetrameric ester bassianolide (PubMed:23608474, PubMed:23727842, PubMed:29163920, PubMed:31388353, PubMed:31471217).
The N-methyltransferase MT domain is responsible for the methylation of the leucine residues of bassianolide (PubMed:29163920, PubMed:31388353).
BSLS is flexible with both the amino acid and hydroxyl acid precursors, and produces bassianolide as the major product (containing N-methyl-L-Leu), together with small amounts of beauvericin and its analogs beauvericins A-C (containing N-methyl-L-Phe) (PubMed:31388353).

Biotechnology

Shows insecticidal activity and contributes to the virulence of the fungus against insects including the corn earworm (Helicoverpa zea), the fall armyworm (Spodoptera exigua) and the greater wax moth (Galleria mellonella) (PubMed:19285149).
Bassianolide possesses antitumor activities and displays significant cytotoxicity against several human tumor cell lines, including A549, SK-OV-3, HepG2, HCT-15, MCF-7 and MDA-MB 231 cell lines with IC50 values of 7.24, 8.44, 15.39, 6.40, 11.42 and 3.98 ug/ml respectively (PubMed:27676608).
Bassianolide especially induces G0/G1 arrest associated with a decrease of cyclin A, D1 and an increase of p53, MDM2, and p21 expression in human breast adenocarcinoma cell lines (PubMed:27676608).

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
0.46 μML-phenylalanyl-N-acetyl-cysteamine thioesterby the MT domain
2.8 μML-leucyl-N-acetyl-cysteamine thioester(by the MT domain)
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
0.41 μM/min/mgtoward L-phenylalanyl-N-acetyl-cysteamine thioester (by the MT domain)
0.05 μM/min/mgtoward L-leucyl-N-acetyl-cysteamine thioester (by the MT domain)

GO annotations

AspectTerm
Cellular Componentcytoplasm
Molecular Functionisomerase activity
Molecular Functionligase activity
Molecular Functionmethyltransferase activity
Molecular Functionphosphopantetheine binding
Biological Processamino acid activation for nonribosomal peptide biosynthetic process
Biological Processmethylation
Biological Processsecondary metabolite biosynthetic process

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Bassianolide nonribosomal cyclodepsipeptide synthetase
  • Short names
    BSLS

Including 2 domains:

  • Recommended name
    Nonribosomal peptide synthetase
  • EC number
  • Recommended name
    S-adenosyl-L-methionine-dependent N-methyltransferase
  • EC number

Gene names

    • Name
      BSLS
    • ORF names
      BBA_02630

Organism names

Accessions

  • Primary accession
    J5JV76

Proteomes

Subcellular Location

Phenotypes & Variants

Disruption phenotype

Abolishes the production of bassianolide but does not affect the biosynthesis of beauvericin (PubMed:19285149).
Attenuates the virulence against insects, including the corn earworm (Helicoverpa zea), the fall armyworm (Spodoptera exigua) and the greater wax moth (Galleria mellonella) (PubMed:19285149).

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00004486651-3147Bassianolide nonribosomal cyclodepsipeptide synthetase
Modified residue1052O-(pantetheine 4'-phosphoryl)serine
Modified residue2549O-(pantetheine 4'-phosphoryl)serine
Modified residue2649O-(pantetheine 4'-phosphoryl)serine

Keywords

Expression

Induction

Expression is induced during insect infection.

Interaction

Protein-protein interaction databases

Structure

3D structure databases

Family & Domains

Features

Showing features for compositional bias, region, domain.

TypeIDPosition(s)Description
Compositional bias1-22Polar residues
Region1-23Disordered
Region69-454Condensation 1
Region495-887Adenylation 1
Domain1015-1091Carrier 1
Region1109-1538Condensation 2
Region1567-1973Adenylation 2
Region2041-2181S-adenosyl-L-methionine-dependent N-methyltransferase (MT)
Domain2515-2589Carrier 2
Domain2615-2689Carrier 3
Region2735-3139Condensation 3

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. Occasionally, additional domains required for further modifications are also present (Probable). Bassianolide synthetase has the C1-A1-T1-C2-A2-MT-T2a-T2b-C3 domain organization. During catalysis, C3 and C2 take turns to incorporate the two biosynthetic precursors into the growing depsipeptide chain that swings between T1 and T2a/T2b with C3 cyclizing the chain when it reaches the full length (PubMed:23727842, PubMed:29163920, PubMed:31388353, PubMed:31471217).
The N-methyltransferase MT domain in module 2 is responsible for the methylation of the leucine residues integrated in the backbone structure (PubMed:29163920, PubMed:31388353).

Sequence similarities

Belongs to the NRP synthetase family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    3,147
  • Mass (Da)
    348,346
  • Last updated
    2012-10-31 v1
  • Checksum
    B8F4C5057B6E0FBA
MEPPNNANTGQLGPTLPNGTVDLPTDLSREITRHFGLEQDEIEEILPCTPFQRDVIECASDDKRRAVGHVVYEIPEDVDTERLAAAWKATVRYTPALRTCIFTSETGNAFQVVLRDCFIFARMYCPSAHLKSAIVKDEATAAVAGPRCNRYVLTGEPNSKRRVLVWTFSHSFVDSAFQGRILQQVLAAYKDEHGRVFSLQPTTDLVESENGDCLSTPASERTVGIERATQFWQEKLHGLDASVFPHLPSHKRVPAIDARADHYLPCPPFIQHEWSSTTVCRTALAILLARYTHSSEALFGVVTEQSHEEHPLLLDGPTSTVVPFRVLCAPNQSVSEVMEAITTYDHDMRQFAHAGLCNISRIGDDASAACGFQTVLMVTDSRTASADEIHHVLEEPEKFIPCTDRALLLSCQMTDEGVLLVARYDQSILEPLQMARFLRQLGFLINKLQSTDGSPCVGQLDVLAPEDRTEIEGWNSEPLQTQDCLIHSEVVKNADDTPNKPAVCAWDGEWTYSELNNVSSRLASYISSLDLGQQLIVPIYLEKSKWVMAAILAVLKAGHAFTLIDPNDPPARTAQIIKQASASIALTSALHQSKMQTVVGRCITVDDDLFQTLTTFEGSQVASAAKPGDLAYVIFTSGSTGDPKGIMIEHRAFYSSVVKFGKALGIRSSTRALQFATHGFGAFLLEVLTTLIHGGCICIPSDHDRMHNIPGFIRQSQINWMMATPSYMTTMKPEDVPGLETLVLVGEQMSSSINDVWLSELQLLDGYGQSESSSICFVGKISDSSRDPNNLGRAIGSHSWIVNPDNPDQLVPIGAIGELLIESPGIARGYLFSQSTETPFLERAPAWYASKQPPYGVKFYRTGDLARYAPDGTVICLGRMDSQVKIRGQRVELDAIENLLRRQFPSDVTVVAEAVKRSDLPSSVVITGFLISSEYVVGAPSTEDTYILDQAVTQEINAKMRQILPAHSIPSFYICMKSLPRTATGKVDRRKLRSIGSSLLALQAQSTAPRSSQAPDASAGVTKLEEVWMDIFNLTPNSHNIGGNFFALGGDSITAIKMVNMARAAGIQLKVSDIFQNPTLASLQAAIGGSSMTVTSIPALALDGPVEQSYSQGRLWFLDQLEIGANWYTIPYAVRLRGPLDVDALNRALLALEKRHETLRTTFEDQDGVGVQIIHETLLDQLRIINADHADYVQLLKQEQTAPFNLASESGWRVSLIRLDDDDNILSIVMHHIISDGWSIDVLRRELGQLYAAALHGADLFGSALSPLPIQYRDFSVWQKQDAQVAEHERQLQYWQKQLADCSPAKLPTDFHRPALLSGKATTVPVTITSELYYRLQEFCSTFNTTSFVVLLATFRAAHYRLTGVDDAVIGTPIANRNRHELENLIGFFVNTQCMRITINEDEETFESLVRQVRSTTTAAFEHEDVPFERVVSAMLPGSRDLSQNPLAQLVFAIHSHKDLGKFELEALESEPLQNEVYTRFDAEFHFFQAPDGLTGYINFATELFKVETIQNVVSVFLQILRHGLEHPQTLISVVPLTDGLAELRSMGLLEIKKVEYPRDSSVVDVFATQVASYPDTLAVVDSSSRLTYAELDHQSDLLATWLRQQNLPTEALVVVLAPRSCETIITFLGILKANLAYLPLDIRSPITRMRDVLSTLPGRTIALLCSDEVAPDFQLPSIELVRIADALEEAAGMTSLNGHEHVPVPSPSPTSLAYVLYTSGSTGRPKGVMIEHRAIVRLARSDIIPDYRPACGDTMAHMFNTAFDGATYEIYTMLLNGGTLVCVDYMDTLSPKSLEAVFKKEQVNATIMAPALLKLYLADARDALKGLDVLISGGDRFDPQDAVDAQSLVRGSCYNGYGPTENGVFSTVYKVDKNDPFVNGVPLGRAVNNSGAYVVDRNQQLVGPGIIGELVVTGDGLARGYTERAFDQNRFIQLKIEGQSVRGYRTGDRVRYRVGEGLIEFFGRMDFQFKIRSNRIEAGEVEAAILSHPAVRNAAVILHVQEKLEPEIVGFVVAEHDDTAEQEEAGDQVEGWQAFFESTTYTELDTVSSSEIGKDFKGWTSMYDGNEIDKAEMQEWLDDTIHTLTDGQALGHVLEIGTGSGMVLFNLGSGLQSFVGLEPSKSAAAFVNNAIKSTPALAGKAHVFVGTATDTNKLDDLHPDLVIFNSVLQYFPTRDYLEQVVDALVHLRSAKRIFFGDVRSYATNRHFLAARAIYTLGNHTTKDEVRKKMAEMEEREEEFLVEPAFFTTLVNRLPDVRHVEIIPKNMQATNELSAYRYAAVVHLRGPDELTRPVHLIKMDDWVDFQASHMHKDALREYLRLAENTKTVAISNIPYGKTIFERQVVESLDDTSEDAPHASLDGAAWISAVRSDAKARSSLSVPDLVLLAKETGFRVEVSAARQWSQSGALDAVFHRYHPAEPDVRTLFQFPTDNDVRMSALLTNQPLQRLQKRRVAVQVREWLQDRIPSYMIPSHIVALDQMPLNTSGKVDRKELSRQAKAIKKVQKSAPPTAPAFPLSEVEVMLCEELTKTFEMDVNITDDFFQLGGHSLLATRLVARISHRLGARLTVKDVFDYPVFSELADIIRQQLASKNTLLPTASAGGGGQDKKESAGVAPTTDMEAMLCEEFANILGMDVGITDNFFDLGGHSLMATRLAARIGHRLNTTISVKDIFSHPVIFQLSAKLEVSQLESSSGGTDIKMPDYTAFQLIPAADAEKFMQDHIYPQINFSQDMVQDVYLATHLQQCFLRDVFGRPKPLVPFYVEFPPDSNPHTLATACTSLVDKYDIFRTIFVEAEGNLYQVVLKHLNLDIDVVETDANVHKTSSDLVDAIAKEPVRLGQPMIQVKVLKQTSSVRVLLWLSHALYDGLSWEHIVRDLHILSKERSLPPATQFSRYMQYVDHTRGPGCDFWRDVLQNAPITNLSDAGSGGRPTKAGDPRVWHAGKVISGPSQAIRSSITQATVFNAACAIVLSKETGTDNVVFGRIVSGRQGLPVRWQNIIGPCTNAVPVRAVVDAHGNHQQMLRDLQEQYLLSLPYETIGFDEIKRSCTDWPDSARNYGCCVTYQNFEYHPESEVDQQRVEMGILAKKAELIKEEPLYNVAIAGEVEPDGVHLQVTVVVDSQLFSQEGATHLMEQVCNTFQALNASL

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias1-22Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
JH725154
EMBL· GenBank· DDBJ
EJP68628.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

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