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Key research themes
1. How can metabolic and synthetic biology strategies optimize isoprenoid biosynthesis pathways in yeast and cyanobacteria for industrial production?
This research area focuses on developing engineered microbial platforms, particularly yeast (Saccharomyces cerevisiae) and cyanobacteria (Synechococcus elongatus), for enhanced production of isoprenoids—a broad class of industrially valuable terpenoids. Important aspects include rewiring central carbon metabolism to optimize precursor acetyl-CoA supply, improving energy/redox balance, balancing competing pathway fluxes, and heterologous expression of key enzymes like isoprene synthase. Constraints addressed involve cofactor specificity, carbon conservation, and pathway bottlenecks relevant for scalable commodity bio-production.
Key finding: This study demonstrates successful metabolic rewiring in Saccharomyces cerevisiae by integrating four non-native enzymatic reactions (phosphoketolase, phosphotransacetylase, acetaldehyde dehydrogenase, and an NADH-specific... Read more
Key finding: This review highlights synthetic biology strategies that augment isoprenoid yields in yeast by engineering central carbon metabolism and the mevalonate (MVA) pathway. Key insights include augmenting acetyl-CoA supply,... Read more
Key finding: This study introduces a metabolic inhibition strategy in cyanobacteria Synechococcus elongatus UTEX 2973, overexpressing heterologous isoprene synthase (IspS) and isopentenyl diphosphate isomerase (IDI), to enhance isoprene... Read more
Key finding: This work demonstrates heterologous expression of plant isoprene synthases (IspSs) in the green microalga Chlamydomonas reinhardtii with plastidic and nuclear localization, enabling direct phototrophic production of volatile... Read more
2. What molecular and enzymatic insights define the specificity and function of key isoprenoid pathway enzymes such as isochorismate synthase, farnesyl diphosphate synthase, and hydroxymethylbutenyl diphosphate synthase?
This research theme investigates the biochemical properties, regulation, and structural determinants of critical enzymes in isoprenoid biosynthesis. Studies include characterization of multiple isozymes (e.g., Arabidopsis thaliana isochorismate synthases ICS1 and ICS2), substrate specificity and active site residues of farnesyl diphosphate synthase (FPPS), and functional amino acids in hydroxymethylbutenyl diphosphate synthase (HDS) governing MEP pathway flux and signaling. Understanding these enzyme functions illuminates pathway regulation, metabolic flux control, and potential drug targeting points.
Key finding: This study biochemically characterizes both Arabidopsis ICS isozymes, AtICS1 and AtICS2, expressed recombinantly. It establishes that AtICS2 is enzymatically active for the first time and reveals both ICS1 and ICS2 require... Read more
Key finding: This comprehensive biochemical review elucidates how specific amino acid residues proximal to the first aspartate-rich motif in farnesyl diphosphate synthase (FPPS) govern product chain length specificity between GPP, FPP,... Read more
Key finding: Through a suppressor screen in Arabidopsis, this study identifies three conserved amino acid substitutions in hydroxymethylbutenyl diphosphate synthase (HDS) that differentially restore phenotypes of a mutant accumulating... Read more
3. How do enzyme structure and reaction mechanisms dictate specialized biosynthesis and functionalization of isoprenoids and related moieties such as isonitriles and isomeric amino acids?
This theme centers on elucidating biosynthetic enzymology of less common isoprenoid-related modifications and analogs critical in natural product diversification and drug discovery. It includes computational and experimental studies on enzymes catalyzing isonitrile formation (e.g., ScoE), chemical and enzymatic pathways to chiral isomers like L-allo-isoleucine, and chemical synthesis routes generating iso-fatty acid derivatives. Insight into these mechanisms deepens understanding of enzyme flexibility, substrate positioning, and catalytic cycles influencing structural complexity in bioactive metabolites.
Key finding: Using computational modeling of the nonheme iron(II)/α-ketoglutarate-dependent dioxygenase ScoE, this study elucidates the stepwise oxidative mechanism converting γ-glycine containing substrates to isonitrile functional... Read more
Key finding: This work identifies and characterizes two enzymatic pairs (DsaD/DsaE and MfnO/MfnH), comprising a pyridoxal 5'-phosphate-dependent aminotransferase and a novel isomerase, responsible for biosynthesis of the rare... Read more
Key finding: This synthetic study delivers efficient, scalable gram-scale methods for terminally-branched iso-fatty acids ranging from C12 to C19, starting from commercially available methyl undecylenate and lactones. The approach... Read more