Table 2.
Summary of Strongest Associations between Syntenic Homologs Present in the Genomic Neighborhood (of the core NR-PKS) and Monophyletic Clades of NR-PKSs
| Clade | Gnode | # | CHG | Description—CHG (Candidate Homolog Group) | P Valuea | Example Accessory Genes |
|---|---|---|---|---|---|---|
| β (azaphilones, meroterpenoids) | g184 | 1 | ch109 | Terpene cyclase | 4E-06 | trt1—Aspergillus terreus terretonin biosynthesis terpene cyclase, ausL—A. nidulans austinol biosynthesis terpene cyclase |
| g204 | 2 | ch71 | Mitochondrial carrier protein (Pfam: Mito_carr) | 3E-05 | — | |
| g273 | 3 | ch73 | YCII superfamily protein (Pfam: YCII) | 8E-07 | dbaC—implicated in biosynthesis of DHMBA (dihydroxy-3-methyl-6-(2-oxopropyl)benzaldehyde) in A. nidulans | |
| g332 | 4 | ch7 | Accessory HR-PKS | 1E-06 | zea2—Fusarium graminearum zearalenone biosynthetic HR-PKS, afoG—A. nidulans asperfuranone biosynthetic HR-PKS | |
| g335 | 5 | ch9 | FAD-binding oxidoreductase | 3E-25 | tropB—Talaromyces stipitatus tropolone biosynthesis FAD monooxygenase, afoD—A. nidulans asperfuranone biosynthesis FAD-dependent oxidase | |
| 6 | ch12 | Zinc-binding oxidoreductase (alcohol dehydrogenase) | 1E-06 | fsr4—F. fujikuroi fusarubin cluster oxidoreductaseb, PMAA_101580—T. marneffei mitorubrinol biosynthesis oxidoreductase | ||
| 7 | ch48 | Acetyltransferase | 2E-09 | PMAA_101560—T. marneffei mitorubrinol biosynthesis acyltransferase | ||
| g336 | 8 | ch20 | FSH1 (serine hydrolase) | 4E-19 | afoC—A. nidulans asperfuranone biosynthesis oxidoreductase, dbaE—A. nidulans DHMBA biosynthesis esterase/lipase | |
| 9 | ch26 | 2-oxoglutarate/Fe(II)-dependent dioxygenase | 7E-11 | tropC—T. stipitatus nonheme iron(II)-dependent dioxygenase involved in tropolone biosynthesis, encD—A. fumigatus dioxygenase involved in endocrocin processing | ||
| g337 | 10 | ch17 | Zinc-finger transcription factor | 3E-24 | rp1—T. marneffei transcriptional activator (red pigment/citrinin cluster), dbaA—A. nidulans DHMBA biosynthesis TF | |
| γ.C2–C7a monocyclic (orsellinic acid, resorcylic acid lactones) | g405 | 11 | ch7 | Accessory HR-PKS | 3E-08 | zea2—F. graminearum zearalenone biosynthetic HR-PKS, afoG—A. nidulans asperfuranone biosynthetic HR-PKS |
| γ.C6–C11 (emodins, atrochrysone, asperthecin) | g454 | 12 | ch46 | Short-chain dehydrogenase (classical SDR subtype) | 3E-05 | mppA—Monascus pilosus azaphilone biosynthesis oxidoreductaseb |
| g490 | 13 | ch68 | Policyclic prenyltransferase (pcPTase) | 6E-10 | dmaT/cpaD—A. flavus cyclopiazonic acid biosynthetic tryptophan dimethylalliltransferase, nscD—Neosartorya fischerii pcPTase involved in neosartoricin biosynthesis | |
| g492 | 14 | ch23 | Zinc-finger transcription factor | 8E-11 | aurR2—F. graminearum aurofusarin biosynthetic TF, nscR—N. fischerii neosartoricin biosynthetic TF | |
| g493 | 15 | ch60 | FAD-binding oxidase (Pfam: FAD_binding_3) | 1E-22 | aptC—A. nidulans asperthecin biosynthetic monooxygenase, nscC—N. fischerii neosartoricin biosynthetic monooxygenase | |
| g494 | 16 | ch32 | FAD-binding oxidase (Pfam: FAD_binding_4) | 8E-07 | — | |
| g548 | 17 | ch36 | Scytalone dehydratase | 5E-08 | arp1—N. fischerii conidial pigment dehydratase, mdpB—A. nidulans dehydratase required for prenylated xanthones' biosynthesis | |
| g549 | 18 | ch18 | Dehydratase (EthD domain) | 1E-09 | aurZ—F. graminearum aurofusarin dehydratase | |
| 19 | ch51 | Domain of unknown function (Pfam: DUF1772) | 1E-05 | aflCa/hypC—A. flavus noranthrone monooxygenase, encC—A. fumigatus endocrocin biosynthetic monooxygenase | ||
| 20 | ch131 | Methyltransferase | 5E-09 | gedD—A. terreus geodin biosynthesis methyltransferase | ||
| g550 | 21 | ch31 | NAD-binding oxidase (Pfam: NAD_binding_10) | 5E-22 | mdpK—A. nidulans oxidoreductase required for prenylated xanthones' biosynthesis, aflI/avfA/stcO—A. flavus averufin oxidase | |
| 22 | ch41 | Baeyer–Villiger oxidase (Pfam: DUF4243) | 3E-07 | mdpL—A. nidulans oxidase required for prenylated xanthones’ biosynthesis, gedK—A. terreus geodin biosynthesis oxidase | ||
| 23 | ch43 | Zinc-finger transcription factor (Pfam: AflR) | 5E-09 | aflR—A. flavus aflatoxin biosynthesis transcription factor, mdpE—A. nidulans monodictyphenone biosynthesis transcription factor | ||
| g552 | 24 | ch14 | β-lactamase | 3E-42 | gedB/ACTE—A. terreus atrochrysone/geodin biosynthesis thioesterase, aptB—A. nidulans asperthecin biosynthesis thioesterase | |
| γ.C2–C7b bicyclic (THN, melanins) | g587 | 25 | ch81 | Prefoldin (chaperone) | 4E-19 | — (housekeeping gene) |
| g623 | 26 | ch125 | Pre-mRNA-splicing factor prp1/6 homolog (proteasome component) | 8E-09 | — (housekeeping gene) | |
| g624 | 27 | ch94 | Imide hydrolase (Pfam: Hydantoinase) | 9E-08 | — | |
| g627 | 28 | ch33 | Zinc-finger transcription factor | 1E-29 | — | |
| γ.C2–C7c multicyclic (naphtopyrone, melanins, aurofusarin, bikaverin) | g669 | 29 | ch130 | Maleylacetate reductase homolog (iron-containing alcohol dehydrogenase) | 2E-10 | — |
| 30 | ch132 | Zinc-finger transcription factor | 7E-08 | — | ||
| g670 | 31 | ch37 | FAD-binding oxidase (Pfam: FAD_binding_3) | 1E-06 | dbaB—A. nidulans FAD-binding monooxygenase implicated in DHMBA biosynthesis | |
| g696 | 32 | ch101 | Multidomain protein (multiple zinc-finger sites, jumonji, ARID domains)—distant homology to histone demethylases (JARID1C; 27% sequence identity) | 4E-09 | — | |
| 33 | ch116 | GIY-YIG nuclease superfamily protein (structure-specific endonuclease subunit slx1 ortholog) | 2E-07 | — (housekeeping gene) | ||
| 34 | ch126 | Glycosyl hydrolase family 31 proteins (∼50% sequence identity to model α-glycoside hydrolases) | 2E-10 | — | ||
| γ.C4–C9 (aflatoxins, sterigmatocystin, fusarubins) | g772 | 35 | ch43 | Zinc-finger transcription factors (Pfam: AflR) | 3E-06 | aflR—A. flavus aflatoxin biosynthesis transcription factor, mdpE—A. nidulans prenylated xanthone biosynthesis TF |
| 36 | ch49 | Accessory FAS—type α | 8E-09 | aflA/fas-2/stcJ—A. flavus fatty acid synthase α (aflatoxin biosynthesis), rp3—Talaromyces marneffei red pigment biosynthesis 3-oxoACP reductase | ||
| 37 | ch54 | Accessory FAS—type β | 1E-07 | aflB/fas-1/stcK—A. flavus fatty acid synthase β (aflatoxin biosynthesis), rp2—T. marneffei red pigment biosynthesis fatty acid synthase β | ||
| g787 | 38 | ch58 | 3-keto-ACP reductase (classical SDR) | 6E-05 | — | |
| 39 | ch85 | Flavin-binding monooxygenase (Pfam: FMO_like) | 6E-06 | aurF—F. graminearum rubrofusarin monooxygenase (aurofusarin biosynthesis) | ||
| g813 | 40 | ch1 | Methyltransferase | 7E-05 | aflO and aflP—A. flavus methyltransferases involved in aflatoxin biosynthesis, fsr2—F. fujikuroi fusarubin biosynthesis methyltransferaseb | |
| γ.C2–C7b/c + γ.C4–C9 | g817 | 41 | ch6 | Laccase (Cu-dependent oxidoreductase) | 1E-06 | abr2—A. fumigatus laccase required for oxidative polymerization of DHN, gip1—F. graminearum laccase dimerizing two 9-hydroxyrubrofusarin molecules (aurofusarin biosynthesis) |
| γ.C6–C11 + γ.C2–C7b/c + γ.C4–C9 | g818 | 42 | ch8 | Enoyl-CoA reductase | 2E-07 | ver1/aflM—A. flavus versicolorin reductase (aflatoxin biosynthesis), 3HNR and 4HNR—Magnaporthe grisea trihydroxynaphtalene and tetrahydroxynaphtalene reductase (melanin biosynthesis)b, mdpC—A. nidulans reductase involved in biosynthesis of monodictyphenone and xanthones |
aPost-Bonferroni correction.
bModel accessory genes from species not covered by the phylogeny reconstruction.