Molecular Enzymology and Evolution
Main research line is the study of the structure-function relationship in enzymes from the viewpoint of understanding the determinants that underlay (thermal)stability and the molecular processes which control the substrate recognition, enzyme inhibition and enzyme catalysis. The tasks are approached mainly by studying enzymes from (hyper)thermophilic sources, mainly from Archaea and are also performed by comparison with mesophilic, homologous counterparts, which allow tracing back evolution of enzyme activity by looking at sequence/structure hallmarks and promiscuous activities. Furthermore, the potential uses of these enzymes in the industry, for the environment and for human health are investigated. Recently focus has been made on some human proteins (PON2, Pyruvate dehydrogenase complex) and their role in many diseases (cancer, type 2 diabetes, atherosclerosis and related complicancies).
Our group’s research focuses on the following topics:
- Study of structure/function relationship, protein-protein interactions and comparative analysis of carboxylesterases belonging to the Hormone Sensitive Lipase (HSL) family from mesophilic, thermophilic and hyperthermophilic sources.
- Study of structure/function relationship and comparative analysis of phosphotriesterases belonging to the amidohydrolase superfamily from mesophilic, thermophilic and hyperthermophilic sources.
- Study of structure/function relationship of PARPSso and comparative analysis from mesophilic, thermophilic and hyperthermophilic sources.
- Application of thermostable carboxylesterases as biosensor and/or traps for organophos- phorous compounds, such as pesticides and nerve agents
- Application of phosphotriesterases from Archaea and soil bacteria as potential agents in decontamination/bioremediation of pesticides
- Tailoring of enzymes to the specific applications listed above through in vitro molecular evolution and structure-driven protein engineering
- Study of the structure/function relationship of human PON2. The protein has been made recombinant in E.coli and insect cells and studied in vitro and in vivo (cells, animal models). Post-translational modifications are investigated by nanoLC-MsMs spectroscopy.
- Modeling, docking analyses and structure resolution (in collaboration) of proteins of interest.
In addition to classical biochemical techniques we also rely on different competencies such as, microbiology, molecular biology, molecular modeling, protein chemistry, protein engineering, directed evolution, enzyme kinetics and inhibition, mass spectrometry and high throughput screening with a robotic workstation. These approaches are complemented with external collaborations in structural biology, protein chemistry, organic chemistry in Italy and abroad as well as strict cooperation with some industries.
- 1987: Graduated in Biological Sciences ”magnacum laudae” at University of Naples.
- 1988-1989: Diploma to exert the profession of Biologist at the University of Naples.
- 1989-1991: Fellowships at International Institute of Genetic and Biophysics (IIGB).
- 1992-1994: Fellowships at Institute of Protein Biochemistry and Enzymology, CNR (National Research Council), Naples.
- 1995: Visitor researcher at National Institute of Health, Bethesda, USA.
- 1994-1997: Contract as non-permanent Researcher (ex art. 23) at the Institute of Protein Biochemistry and Enzymology, CNR (National Research Council), Naples
- 1997-2001: Contract as permanent Staff Researcher at the Institute of Protein Biochemistry and enzymology, CNR (National Research Council), Naples
- 2001-till now: Contract as permanent Senior Staff Researcher at the Institute of Protein Biochemistry of CNR of Italy.
- 2014- National Scientific Qualification (ASN) as full professor in Biochemistry
- 2019- National Scientific Qualification (ASN) as full professor in Molecular Biology
- 2019- Nominated national delegate for INPEC (International Network of Protein Engineering Centers)
Mandrich L., Porzio E., Manco G. (Inventors). Mutanti della paraoxonasi 2 umana e sue formulazioni per la degradazione di differenti composti organo(tio)fosfati.
Released Italian Patent N. UB2015A002032.
Manco G, Porzio E, Febbraio F, Carusone TM, Palchetti I. (Inventors) SISTEMA INTEGRATO PER LA RILEVAZIONE E DEGRADAZIONE DI AGENTI NERVINI MEDIANTE BIOCATALIZZATORI TERMOSTABILI
Released Italian Patent N. 102015000027699.
Cetrangolo GP, Gori C, Rusko J, Sara Terreri , Giuseppe Manco, Amelia Cimmino, Ferdinando Febbraio.
Determination of Picomolar Concentrations of Paraoxon in Human Urine by Fluorescence-Based Enzymatic Assay. Sensors (Basel). 2019;19(22):4852. Published 2019 Nov 7. doi:10.3390/s19224852
Elena Porzio, Francesca Bettazzi , Luigi Mandrich, Immacolata Del Giudice, Odile F Restaino , Serena Laschi , Ferdinando Febbraio , Valentina De Luca, Maria G Borzacchiello , Teresa M Carusone, Franz Worek, Antonio Pisanti, Piero Porcaro , Chiara Schiraldi, Mario De Rosa, Ilaria Palchetti , Giuseppe Manco
Innovative Biocatalysts as Tools to Detect and Inactivate Nerve Agents. Sci Rep. 2018;8(1):13773. Published 2018 Sep 13. doi:10.1038/s41598-018-31751-5
Ferriero R, Nusco E, De Cegli R, Carissimo A, Manco G, Brunetti-Pierri N. Pyruvate dehydrogenase complex and lactate dehydrogenase are targets for therapy of acute liver failure. J Hepatol. 2018;69(2):325–335. doi:10.1016/j.jhep.2018.03.016
Ferriero R, Manco G, Lamantea E, Edoardo Nusco, Maria I Ferrante, Paolo Sordino, Peter W Stacpoole, Brendan Lee, Massimo Zeviani, Nicola Brunetti-Pierri.
Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis. Sci Transl Med. 2013;5(175):175ra31. doi:10.1126/scitranslmed.3004986
Elias M, Dupuy J, Merone L, Mandrich L, Porzio E, Moniot S, Rochu d, Lecomte C, Rossi M, Masson P, Manco G, Chabriere E (2008)
“Structural basis for natural lactonase and promiscuous phosphotriesterase activities” Journal of Molecular Biology 379:1017-1028.
Last five years
- Biocatalytic membrane reactor development for organophosphates degradation Vitola G, et al. J Hazard Mater 2019. Among authors: Manco G. PMID 30476802
- Cetrangolo GP, et al. Sensors (Basel) 2019. Determination of Picomolar Concentrations of Paraoxon in Human Urine by Fluorescence-Based Enzymatic Assay Among authors: Manco G. PMID 31703397 Free PMC article.
- Porzio E, Bettazzi F, Mandrich L, Del Giudice I, Restaino OF, Laschi S, Febbraio F, De Luca V, Borzacchiello MG, Carusone TM, Worek F, Pisanti A, Porcaro P, Schiraldi C, De Rosa M, Palchetti I, Manco G. Innovative Biocatalysts as Tools to Detect and Inactivate Nerve Agents. Sci Rep. 2018 Sep 13;8(1):13773. doi: 10.1038/s41598-018-31751-5.
- Ferriero R, Nusco E, De Cegli R, Carissimo A, Manco G, Brunetti-Pierri N. Pyruvate dehydrogenase complex and lactate dehydrogenase are targets for therapy of acute liver failure. J Hepatol. 2018 Aug;69(2):325-335. doi: 10.1016/j.jhep.2018.03.016. Epub 2018 Mar 24.
- Manco G, Porzio E and Suzumoto Y Enzymatic detoxification: a sustainable means of degrading toxic organophosphate pesticides and chemical warfare nerve agents J Chem Technol Biotechnol (2018) (wileyonlinelibrary.com) DOI 10.1002/jctb.5603
- Carullo Paola; Chino, Marco; Cetrangolo, Giovanni Paolo; Terreri, Sara; Lombardi, Angelina; Manco, Giuseppe; Cimmino, Amelia; Febbraio, Ferdinando SENSORS AND ACTUATORS. B, CHEMICAL 2018 255, 3257-3266
- Porzio E, De Maio A, Ricciardi T, Mistretta C, Manco G, Faraone-Mennella MR. Comparison of the DING protein from the archaeon Sulfolobus solfataricus with human phosphate-binding protein and Pseudomonas fluorescence DING counterparts. Extremophiles. 2018 22:177-188.
- Restaino OF, Borzacchiello MG, Scognamiglio I, Fedele L, Alfano A, Porzio E, Manco G, De Rosa M, Schiraldi C. High yield production and purification of two recombinant thermostable phosphotriesterase-like lactonases from Sulfolobus acidocaldarius and Sulfolobus solfataricus useful as bioremediation tools and bioscavengers. BMC Biotechnol. 2018 Mar 20;18(1):18.
- Ferriero R, Nusco E, De Cegli R, Carissimo A, Manco G, Brunetti-Pierri N. Pyruvate dehydrogenase complex and lactate dehydrogenase are targets for therapy of acute liver failure. J Hepatol. 2018 Mar 24. pii: S0168-8278(18)30210-1.
- Gebreyohannes AY, Mazzei R, Marei Abdelrahim MY, Vitola G, Porzio E, Manco G, Barboiu M, Giorno L. Phosphotriesterase-Magnetic Nanoparticle Bioconjugates with Improved Enzyme Activity in a Biocatalytic Membrane Reactor. Bioconjug Chem. 2018 Jun 20;29(6):2001-2008.
- Restaino O.F · Borzacchiello MG · Scognamiglio I Porzio E· Manco G · Fedele L · Donatiello C · De Rosa M · Schiraldi C Boosted large-scale production and purification of a thermostable archaeal phosphotriesterase-like lactonase for organophosphate decontamination J Ind Microbiol Biotechnol 2017 44(3):363-375.
- Manco G New Insight in Human Lactonase PON2 Biomed J Sci & Tech Res 2017 DOI:10.26717/BJSTR. 2017.01.000424
- G. Vitola, R. Mazzei, E. Fontananova, E. Porzio, G. Manco, S.N. Gaeta and L. Giorno Polymeric biocatalytic membranes with immobilized thermostable phosphotriesterase Journal of Membrane Science, 2016 DOI: 10.1016/j.memsci. 2016.06.020
- Sirangelo I, Vella F M., Irace G, Manco G and Iannuzzi C Glycation in Demetalated Superoxide Dismutase 1 Prevents Amyloid Aggregation and Produces Cytotoxic Ages Adducts Front. Mol. Biosci., 16;3:55. eCollection 2016.| http://dx.doi.org/10.3389/fmolb.2016.00055.
- Mandrich L, Cerreta M, Manco G. An Engineered Version of Human PON2 Opens the Way to Understand the Role of Its Post-Translational Modifications in Modulating Catalytic Activity. PLoS One. 2015 Dec 10;10(12):e0144579. doi: 10.1371/journal.pone.0144579. eCollection 2015.
- Del Giudice I, Coppolecchia R, Merone L, Porzio E, Carusone TM, Mandrich L, Worek F, Manco G. An efficient thermostable organophosphate hydrolase and its application in pesticide decontamination. Biotechnol Bioeng. 2015 Sep 29. doi: 10.1002/bit.25843.
- Elena Porzio, Immacolata Del Giudice, Giuseppe Manco. Engineering of Extremophilic Phosphotriesterase-Like Lactonases for Biotechnological Applications. 2015 accepted review Springer “Botechnology of Extremophiles”.
- Zhang Y, An J, Yang GY, Bai A, Zheng B, Lou Z, Wu G, Ye W, Chen HF, Feng Y, Manco G. Active site loop conformation regulates promiscuous activity in a lactonase from Geobacillus kaustophilus HTA426 PLoS One. 2015 Feb 23;10(2):e0115130.
- Carullo P, Cetrangolo GP, Mandrich L, Manco G, Febbraio F. Fluorescence spectroscopy approaches for the development of a real-time organophosphate detection system using an enzymatic sensor. Sensors (Basel). 2015 Feb 9;15(2):3932-51.
- Ferriero R, Iannuzzi C, Manco G, Brunetti-Pierri N. Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate dehydrogenase complex activity by combination with dichloroacetate. J Inherit Metab Dis. 2015 Jan 20.
- Zhang Y, An J, Yang GY, Bai A, Zheng B, Lou Z, Wu G, Ye W, Chen HF, Rao Z, Feng Y, Manco G (2015) Active site loop conformation regulates promiscuous activity in a lactonase from Geobacillus kaustophilus HTA426. PLoS One. Feb 23;10(2):e0115130
- PON 01_01585 PRODOTTI INNOVATIVI PER IL MONITORAGGIO E LA DECONTAMINAZIONE / DETOSSIFICAZIONE DI AGENTI NERVINI ED ESPLOSIVI NELL’AMBIENTE E/O PER LA GESTIONE DELLE EMERGENZE
- POR CAMPANIA FESR Nuove strategie per la diagnostica medica e molecolare e per la tracciabilità ed il monitoraggio dei prodotti alimentari ” 2014-2020.
- “Proof of Concept” MIUR– “Innovative anti-biofilm systems for wound infections” 2019-2021.
- EU 2020 “DNA helicases in genome maintenance: from molecular and cellular mechanisms to specific inhibitors as potential drugs”.
Il Miur finanzia ‘Siabio’, il nuovo progetto di ricerca ‘proof of concept’ di Cnr-Ibbc
Un progetto del Sud come supporto alle emergenze che vedono coinvolti agenti neurotossici
L’Italia dei giovani leader del futuro: dottoranda Cnr-Ibp menzionata da Forbes
Due borse Fulbright BEST all’IBP CNR di Napoli
15 idee per il futuro. Ecco i progetti finalisti del premio Start-Cup 2011 organizzato da Cnr e Il Sole