Proteomic insights on the metabolism of Penicillium janczewskii during the biotransformation of the plant terpenoid labdanolic acid

Isabel Martins, Adélia Varela, Luís M.T. Frija, Mónica A.S. Estevão, Sébastien Planchon, Jenny Renaut, Carlos A.M. Afonso, Cristina Silva Pereira

Research output: Contribution to journalArticle

Abstract

Plant terpenoids compose a natural source of chemodiversity of exceptional value. Many of these compounds own biological/pharmacological activity, others are regarded as unique chemical skeletons for the synthesis of derivatives with improved properties. Functional chemical modification of terpenoids through biotransformation frequently relies on the use of Ascomycota strains, but information on major cellular responses is still largely lacking. Penicillium janczewskii mediates a stereo-selective hydroxylation of labdanolic acid (LA)-terpenoid found abundantly in Cistus ladanifer-producing 3β-hydroxy-labdanolic acid with yields > 90%. Herein, combined analyses of mycelial and extracellular differential proteomes demonstrated that the plant terpenoid increased stress responses, especially against oxidative stress (e.g., accumulation of superoxide dismutase) and apparently altered mitochondria functioning. One putative cytochrome P450 monooxygenase differentially accumulated in the secretome and the terpenoid bioconversion was inhibited in vivo in the presence of a P450 inhibitor. The stereo-selective hydroxylation of the plant terpenoid is likely mediated by P450 enzymes, yet its unequivocal identity remains unclear. To the best of our knowledge, this is the first time that proteomics was used to investigate how a plant terpenoid impacts the metabolism of a filamentous fungus during its efficiently biotransformation. Our findings may encourage the development of new strategies for the valorization of plant natural resources through biotechnology.

Original languageEnglish
Article number45
JournalFrontiers in Bioengineering and Biotechnology
Volume5
Issue numberAUG
DOIs
Publication statusPublished - 31 Jul 2017

Fingerprint

Hydroxylation
Penicillium
Terpenes
Biotransformation
Metabolism
Proteomics
Bioconversion
Mitochondria
Acids
Oxidative stress
Chemical modification
Natural resources
Biotechnology
Bioactivity
Fungi
Derivatives
Proteins
Cytochrome P-450 Enzyme System
Cistus
Ascomycota

Keywords

  • Cytochrome P450 monooxygenase
  • Labdanolic acid
  • Penicillium janczewskii
  • Proteomics
  • Stress response
  • Terpenoids biotransformation

Cite this

@article{88814b3662fe4853b8fa072187e079b6,
title = "Proteomic insights on the metabolism of Penicillium janczewskii during the biotransformation of the plant terpenoid labdanolic acid",
abstract = "Plant terpenoids compose a natural source of chemodiversity of exceptional value. Many of these compounds own biological/pharmacological activity, others are regarded as unique chemical skeletons for the synthesis of derivatives with improved properties. Functional chemical modification of terpenoids through biotransformation frequently relies on the use of Ascomycota strains, but information on major cellular responses is still largely lacking. Penicillium janczewskii mediates a stereo-selective hydroxylation of labdanolic acid (LA)-terpenoid found abundantly in Cistus ladanifer-producing 3β-hydroxy-labdanolic acid with yields > 90{\%}. Herein, combined analyses of mycelial and extracellular differential proteomes demonstrated that the plant terpenoid increased stress responses, especially against oxidative stress (e.g., accumulation of superoxide dismutase) and apparently altered mitochondria functioning. One putative cytochrome P450 monooxygenase differentially accumulated in the secretome and the terpenoid bioconversion was inhibited in vivo in the presence of a P450 inhibitor. The stereo-selective hydroxylation of the plant terpenoid is likely mediated by P450 enzymes, yet its unequivocal identity remains unclear. To the best of our knowledge, this is the first time that proteomics was used to investigate how a plant terpenoid impacts the metabolism of a filamentous fungus during its efficiently biotransformation. Our findings may encourage the development of new strategies for the valorization of plant natural resources through biotechnology.",
keywords = "Cytochrome P450 monooxygenase, Labdanolic acid, Penicillium janczewskii, Proteomics, Stress response, Terpenoids biotransformation",
author = "Isabel Martins and Ad{\'e}lia Varela and Frija, {Lu{\'i}s M.T.} and Estev{\~a}o, {M{\'o}nica A.S.} and S{\'e}bastien Planchon and Jenny Renaut and Afonso, {Carlos A.M.} and Pereira, {Cristina Silva}",
year = "2017",
month = "7",
day = "31",
doi = "10.3389/fbioe.2017.00045",
language = "English",
volume = "5",
journal = "Frontiers in Bioengineering and Biotechnology",
issn = "2296-4185",
publisher = "Frontiers Media",
number = "AUG",

}

Proteomic insights on the metabolism of Penicillium janczewskii during the biotransformation of the plant terpenoid labdanolic acid. / Martins, Isabel; Varela, Adélia; Frija, Luís M.T.; Estevão, Mónica A.S.; Planchon, Sébastien; Renaut, Jenny; Afonso, Carlos A.M.; Pereira, Cristina Silva.

In: Frontiers in Bioengineering and Biotechnology, Vol. 5, No. AUG, 45, 31.07.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Proteomic insights on the metabolism of Penicillium janczewskii during the biotransformation of the plant terpenoid labdanolic acid

AU - Martins, Isabel

AU - Varela, Adélia

AU - Frija, Luís M.T.

AU - Estevão, Mónica A.S.

AU - Planchon, Sébastien

AU - Renaut, Jenny

AU - Afonso, Carlos A.M.

AU - Pereira, Cristina Silva

PY - 2017/7/31

Y1 - 2017/7/31

N2 - Plant terpenoids compose a natural source of chemodiversity of exceptional value. Many of these compounds own biological/pharmacological activity, others are regarded as unique chemical skeletons for the synthesis of derivatives with improved properties. Functional chemical modification of terpenoids through biotransformation frequently relies on the use of Ascomycota strains, but information on major cellular responses is still largely lacking. Penicillium janczewskii mediates a stereo-selective hydroxylation of labdanolic acid (LA)-terpenoid found abundantly in Cistus ladanifer-producing 3β-hydroxy-labdanolic acid with yields > 90%. Herein, combined analyses of mycelial and extracellular differential proteomes demonstrated that the plant terpenoid increased stress responses, especially against oxidative stress (e.g., accumulation of superoxide dismutase) and apparently altered mitochondria functioning. One putative cytochrome P450 monooxygenase differentially accumulated in the secretome and the terpenoid bioconversion was inhibited in vivo in the presence of a P450 inhibitor. The stereo-selective hydroxylation of the plant terpenoid is likely mediated by P450 enzymes, yet its unequivocal identity remains unclear. To the best of our knowledge, this is the first time that proteomics was used to investigate how a plant terpenoid impacts the metabolism of a filamentous fungus during its efficiently biotransformation. Our findings may encourage the development of new strategies for the valorization of plant natural resources through biotechnology.

AB - Plant terpenoids compose a natural source of chemodiversity of exceptional value. Many of these compounds own biological/pharmacological activity, others are regarded as unique chemical skeletons for the synthesis of derivatives with improved properties. Functional chemical modification of terpenoids through biotransformation frequently relies on the use of Ascomycota strains, but information on major cellular responses is still largely lacking. Penicillium janczewskii mediates a stereo-selective hydroxylation of labdanolic acid (LA)-terpenoid found abundantly in Cistus ladanifer-producing 3β-hydroxy-labdanolic acid with yields > 90%. Herein, combined analyses of mycelial and extracellular differential proteomes demonstrated that the plant terpenoid increased stress responses, especially against oxidative stress (e.g., accumulation of superoxide dismutase) and apparently altered mitochondria functioning. One putative cytochrome P450 monooxygenase differentially accumulated in the secretome and the terpenoid bioconversion was inhibited in vivo in the presence of a P450 inhibitor. The stereo-selective hydroxylation of the plant terpenoid is likely mediated by P450 enzymes, yet its unequivocal identity remains unclear. To the best of our knowledge, this is the first time that proteomics was used to investigate how a plant terpenoid impacts the metabolism of a filamentous fungus during its efficiently biotransformation. Our findings may encourage the development of new strategies for the valorization of plant natural resources through biotechnology.

KW - Cytochrome P450 monooxygenase

KW - Labdanolic acid

KW - Penicillium janczewskii

KW - Proteomics

KW - Stress response

KW - Terpenoids biotransformation

UR - http://www.scopus.com/inward/record.url?scp=85040761605&partnerID=8YFLogxK

U2 - 10.3389/fbioe.2017.00045

DO - 10.3389/fbioe.2017.00045

M3 - Article

VL - 5

JO - Frontiers in Bioengineering and Biotechnology

JF - Frontiers in Bioengineering and Biotechnology

SN - 2296-4185

IS - AUG

M1 - 45

ER -