Jerry Ståhlberg is biochemist, Associate professor in Molecular Biology and researcher at Department of Molecular Sciences, SLU. We express and purify proteins, characterize biochemically, measure enzyme activities, study 3D structures with X-ray crystallography, and evaluate for various biotechnical purposes. One major focus area concerns cellulases and other enzymes from plant degrading fungi and bacteria that are or can be useful for production of biofuels and other chemicals from lignocellulosic biomass.
At undergraduate level I teach general biochemistry and lecture on protein structure and carbohydrates. I have also organized the PhD courses “Processing biomass for biofuels and chemicals”, “Protein structure hands-on workshop” and “Protein crystallization and X-ray data collection”, and lecture occasionally on other PhD and Master courses, internally at SLU and externally, on e.g. protein structure, wood degrading fungi, industrial enzymes and biomass-to-biofuel conversion.
Basic research on protein structure and function using X-ray crystallography plays a central role and we have deposited over 100 structures at the Protein Data Bank (PDB). One focus area concerns carbohydrate active enzymes where we have investigated structure and function of key enzymes from fungi and bacteria that degrade cellulose and other polysaccharides. The results pave the way for improved enzymes and industrial processes for biofuel production through enzyme engineering and genome mining.
Major research topics at present are:
GH7 cellulases – Molecular function and diversity
Fungi are responsible for the majority of plant biomass recycling in terrestrial ecosystems. The most abundant enzymes and major workhorses in cellulose degradation belong to glycoside hydrolase family 7 (GH7). They are also the major components in industrial cellulase cocktails. We have investigated and know rather well how fungal GH7 enzymes look and work. However, GH7s are also present in distantly related organisms (e.g. crustaceans, oomycetes, dinoflagellates). We have earlier determined structure and function of such enzymes in social amoeba (Dictyostelium sp). Now we study GH7 cellulases of symbiotic protozoa (Parabasalia) that live in the gut of termites and enable them to eat wood.
Expansins, loosenins, GH45 – Catalytic mechanism(s)
All plants need proteins called expansins to be able to grow. Expansins are known to loosen up the cell wall so that plant cells can expand several-fold in size after cell division. However, how they do this at molecular level has remained elusive. That is what we want to find out. Expansin homologs with similar structure and catalytic center are used as model proteins, so called loosenins that seem to soften cell walls without hydrolysis, and GH45 enzymes that can cleave glycosidic bonds by hydrolysis. Their interactions with carbohydrates are analyzed in detail using advanced NMR techniques.
Transaminases – Functionalization of carbohydrates through amination
This project is a collaboration with Alto University, Finland, Toronto University, Canada, and Doc. Mats Sandgren and Gustav Nestor at our department. Certain transaminases can be used to attach amino groups on carbohydrates that in turn function as handles for chemical modification, towards functionalization of hemicellulose polysaccharides to novel biobased materials. Our role is to determine structures of transaminases with bound carbohydrates to find structural determinants for substrate specificity and enzyme efficiency and thereby pave the way for rational design of tailored enzymes through protein engineering.
Metacaspases – Structure, activation, specificity and regulation
Metacaspases is a diverse family of cysteine proteases and evolutionary ancestors of the well-studied caspases in humans and other animals. Metacaspases are spanning all kingdoms of life, with essential roles in cell death and differentiation, clearance of protein aggregates and aging. However, molecular mechanisms of metacaspase activation, specificity and regulation remain largely unknown, making it difficult to understand metacaspase-guided processes and their potential application in biotechnology and medicine. These questions are addressed in a five-year research program supported by the Knut and Alice Wallenberg foundation, where we are responsible for expression and purification of metacaspases, biochemical characterization, crystallization and structure studies. The programme involves five research groups at SLU and Umeå University, and is lead by Prof. Peter Bozhkov, Dept. Molecular Sciences, SLU.
Jerry Ståhlberg is appointed as external collaboration specialist in microbial processes for conversion of biomass to biofuels other than biogas. He is also member of the steering board of two research schools at SLU, Focus on Food and Biomaterials, and Sustainable Biomass Systems.
I am originally from Karlstad, Värmland, in the west of Sweden and came to Uppsala in the 1980’s. At Uppsala University I got a BSc in Biology and PhD in Biochemistry (with Doc. Göran Petterson) on a thesis entitled “Functional organization of cellulases from Trichoderma reesei”. I was then recruited to the structural biology group of Prof. Alwyn Jones, Dept. Molecular Biology, UU, and learned protein crystallization and structure determination with X-ray crystallography, which has been central to my research ever since. In 1998 I became Docent (Associate professor) in Molecular Biology, moved to SLU (Dept Molecular Biology), received own research grants and got my first PhD student as main supervisor. Since then, I work as researcher, supervisor and teacher at SLU. I was also 20% guest researcher for four years (2009-2013) at Norwegian University of Life Sciences, Ås, Norway (NMBU). Year 2013 our department (Molecular Biology, SLU) moved from Uppsala Biomedical Centre (BMC) to SLU-Biocenter at Ultuna. We joined first with Dept of Chemistry, and then in 2017 with Dept Microbiology and Dept Food Science, to form the current Dept Molecular Sciences.
Main supervisor for five graduated (Ines Muñoz, 2002; Jonas Vasur, 2009; Miao Wu, 2013; Majid Haddad Momeni, 2014; Anna Borisova, 2017) and two ongoing PhD students (Topi Haataja; Laura Okmane). Co-supervisor for 12 graduated PhD students. Supervisor or examiner for >20 MSc and BSc projects.
Bibliometric summary:
77 articles in peer-reviewed journals (1988-2021); 8444 citations;
h-index 43; i10-index 75 (Google Scholar citation metrics 20211213)
Okmane L, Nestor G, Jakobsson E, Xu B, Igarashi K, Sandgren M, Kleywegt GJ, Ståhlberg J (2021) Glucomannan and beta-glucan degradation by Mytilus edulis Cel45A: Crystal structure and activity comparison with GH45 subfamily A, B and C. Carbohydrate Polymers 277, 118771.
Gado JE, Harrison BE, Sandgren M, Ståhlberg J, Beckham GT, Payne CM (2021) Machine learning reveals sequence-function relationships in family 7 glycoside hydrolases. J Biol Chem 297, 100931.
Levenfors JJ, Nord C, Bjerketorp J, Ståhlberg J, Larsson R, Guss B, Öberg B, Broberg A (2020) Antibacterial pyrrolidinyl and piperidinyl substituted 2,4-diacetylphloroglucinols from Pseudomonas protegens UP46. J Antibiot (Tokyo) 73, 739-747.
Bharadwaj VS, Knott BC, Ståhlberg J, Beckham GT, Crowley MF (2020) The hydrolysis mechanism of a GH45 cellulase and its potential relation to lytic transglycosylase and expansin function. J Biol Chem 295, 4477-4487.
Minina EA, Staal J, Alvarez VE, Berges JA, Berman-Frank I, Beyaert R, Bidle KD, Bornancin F, Casanova M, Cazzulo JJ, Choi CJ, Coll NS, Dixit VM, Dolinar M, Fasel N, Funk C, Gallois P, Gevaert K, Gutierrez-Beltran E, Hailfinger S, Klemenčič M, Koonin EV, Krappmann D, Linusson A, Machado MFM, Madeo F, Megeney LA, Moschou PN, Mottram JC, Nyström T, Osiewacz HD, Overall CM, Pandey KC, Ruland J, Salvesen GS, Shi Y, Smertenko A, Stael S, Ståhlberg J, Suárez MF, Thome M, Tuominen H, Van Breusegem F, van der Hoorn RAL, Vardi A, Zhivotovsky B, Lam E, Bozhkov PV (2020) Classification and Nomenclature of Metacaspases and Paracaspases: No More Confusion with Caspases. Mol Cell 77, 927-929.
Vermaas JV, Kont R, Beckham GT, Crowley MF, Gudmundsson M, Sandgren M, Ståhlberg J, Väljamäe P, Knott BC (2019) The dissociation mechanism of processive cellulases. Proc Natl Acad Sci USA 116,23061-23067.
Hamark C, Pendrill R, Landström J, Dotson Fagerström A, Sandgren M, Ståhlberg J, Widmalm G (2018) Enantioselective Binding of Propranolol and Analogues Thereof to Cellobiohydrolase Cel7A. Chem Eur J 24, 17975-17985.
Liu B, Krishnaswamyreddy S, Muraleedharan MN, Olson Å, Broberg A, Ståhlberg J, Sandgren M (2018) Side-by-side biochemical comparison of two lytic polysaccharide monooxygenases from the white-rot fungus Heterobasidion irregulare on their activity against crystalline cellulose and glucomannan. PLoS One 13, e0203430.
Burgin T, Ståhlberg J, Mayes HB (2018) Advantages of a Distant Cellulase Catalytic Base. J Biol Chem 293, 4680-4687.
Borisova AS, Eneyskaya EV, Jana S, Badino SF, Kari J, Amore A, Karlsson M, Hansson H, Sandgren M, Himmel ME, Westh P, Payne CM, Kulminskaya AA, Ståhlberg J (2018) Correlation of structure, function and protein dynamics in GH7 cellobiohydrolases from Trichoderma atroviride, T. reesei and T. harzianum. Biotechnology for Biofuels 11, 5.
Goedegebuur F, Dankmeyer L, Gualfetti P, Karkehabadi S, Hansson H, Jana S, Huynh V, Kelemen BR, Kruithof P, Larenas EA, Teunissen PJM, Ståhlberg J, Payne CM, Mitchinson C, Sandgren M (2017) Improving the thermal stability of cellobiohydrolase Cel7A from Hypocrea jecorina by directed evolution. J Biol Chem 292, 17418-17430.
Chylenski P, Forsberg Z, Ståhlberg J, Várnai A, Lersch M, Bengtsson O, Sæbø S, Horn SJ, Eijsink VG (2017) Development of minimal enzyme cocktails for hydrolysis of sulfite-pulped lignocellulosic biomass. J Biotechnol 246, 16-23.
Mayes HB, Knott BC, Crowley MF, Broadbelt LJ, Ståhlberg J, Beckham GT (2016) Who's on base? Revealing the catalytic mechanism of inverting family 6 glycoside hydrolases. Chemical Science 7, 5955-5968.
Hobdey SE, Knott BC, Haddad Momeni M, Taylor II LE, Borisova AS, Podkaminer KK, VanderWall TA, Himmel ME, Decker SR, Beckham GT, Ståhlberg J (2016) Biochemical and structural characterization of two Dictyostelium cellobiohydrolases from the Amoebozoa kingdom reveal a high conservation between distant phylogenetic trees of life. Appl Environ Microbiol 82, 3395-3409.
Borisova AS, Eneyskaya EV, Bobrov KS, Jana S, Logachev A, Polev DE, Lapidus AL, Ibatullin FM, Saleem U, Sandgren M, Payne CM, Kulminskaya AA, Ståhlberg J (2015) Sequencing, biochemical characterization, crystal structure and molecular dynamics of cellobiohydrolase Cel7A from Geotrichum candidum 3C. FEBS J 282, 4515-4537.
Haddad Momeni M, Ubhayasekera W, Sandgren M, Ståhlberg J, Hansson H (2015) Structural insights into the inhibition of Cellobiohydrolase Cel7A by xylooligosaccharides. FEBS J 282, 2167-2177.
Payne CM, Knott BC, Mayes HB, Hansson H, Himmel ME, Sandgren M, Ståhlberg J, Beckham GT (2015) Fungal cellulases. Chem Rev 115, 1308-1448.