Mauro A. Rinaldi

University of Manchester

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Bonnie Bartel

Rice University

Sarah E. Burkhart

Rice University

Lisa M. Farmer

Children's Nutrition Research Center at Baylor College of Medicine

Ashish Patel

Kamdhenu University

Lucia C. Strader

Washington University in St. Louis

Pierce G. Young

Texas A&M University

Nigel S. Scrutton

University of Manchester

Charles Danan

Children's Hospital of Philadelphia

Margherita Melegari

University of Cincinnati Medical Center

Ko-Eun Lee

University of Ulsan

Cooperative Institutions

Rice University

University of Buenos Aires

Consejo Nacional de Investigaciones Científicas y Técnicas

University of York

University of Modena and Reggio Emilia

Experimental Medicine and Biology Institute

University of Minnesota

University of North Texas

Czech Academy of Sciences, Institute of Biotechnology

University of Manchester

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

[Molecular structure with potential inhibitory action on the biosynthesis of FAH4].

PubMed (1983)

P Pecorari G Vampa A Albasini Mauro A. Rinaldi Margherita Melegari

Molecules formed by two pharmacophoric synthons--4-H2N--C6H4--SO2NH--and 2,4-diaminopyrimidine--were prepared. These structural units, with sulphamidic and antifolic action respectively, are bound without mutual electronic interaction, as demonstrated by their experimental electronic indices. The compounds were tested for activity on several bacterial strains and their biological activity was compared with that of molecular combinations formed by 4-aminobenzensulphonamide and substituted 2,4-diaminopyrimidines, to discover whether these two pharmacophoric synthons, so bound, are synergic.

Synthon

Molecular model

Source

Cite

Citations (0)

Incentive or Habit Learning in Amphibians?

PLoS ONE (2011)

Rubén N. Muzio Virginia Pistone Creydt Mariana Gabriela Iurman Mauro A. Rinaldi Bruno Sirani

Toads (Rhinella arenarum) received training with a novel incentive procedure involving access to solutions of different NaCl concentrations. In Experiment 1, instrumental behavior and weight variation data confirmed that such solutions yield incentive values ranging from appetitive (deionized water, DW, leading to weight gain), to neutral (300 mM slightly hypertonic solution, leading to no net weight gain or loss), and aversive (800 mM highly hypertonic solution leading to weight loss). In Experiment 2, a downshift from DW to a 300 mM solution or an upshift from a 300 mM solution to DW led to a gradual adjustment in instrumental behavior. In Experiment 3, extinction was similar after acquisition with access to only DW or with a random mixture of DW and 300 mM. In Experiment 4, a downshift from DW to 225, 212, or 200 mM solutions led again to gradual adjustments. These findings add to a growing body of comparative evidence suggesting that amphibians adjust to incentive shifts on the basis of habit formation and reorganization.

Extinction (optical mineralogy)

Habit

10.1371/journal.pone.0025798

Cite

Citations (29)

Flavonoid Versus Artemisinin Anti-malarial Activity in Artemisia annua Whole-Leaf Extracts

Frontiers in Plant Science (2019)

Tomasz Czechowski Mauro A. Rinaldi Mufuliat Toyin Famodimu Maria Van Veelen Tony R. Larson

Artemisinin, a sesquiterpene lactone produced by Artemisia annua glandular secretory trichomes, is the active ingredient in the most effective treatment for uncomplicated malaria caused by Plasmodium falciparum parasites. Other metabolites in A. annua or related species, particularly flavonoids, have been proposed to either act as antimalarials on their own or act synergistically with artemisinin to enhance antimalarial activity. We identified a mutation that disrupts the CHALCONE ISOMERASE 1 (CHI1) enzyme that is responsible for the second committed step of flavonoid biosynthesis. Detailed metabolite profiling revealed that chi1-1 lacks all major flavonoids but produces wild-type artemisinin levels, making this mutant a useful tool to test the antiplasmodial effects of flavonoids. We used whole-leaf extracts from chi1-1 and mutant lines impaired in artemisinin production in bioactivity in vitro assays against intraerythrocytic P. falciparum Dd2. We found that chi1-1 extracts did not differ from wild-type extracts in antiplasmodial efficacy nor initial rate of cytocidal action. Furthermore, extracts from the A. annua cyp71av1-1 mutant and RNAi lines impaired in amorpha-4,11-diene synthase gene expression, which are both severely compromised in artemisinin biosynthesis but unaffected in flavonoid metabolism, showed very low or no antiplasmodial activity. These results demonstrate that in vitro bioactivity against P. falciparum of flavonoids is negligible when compared to that of artemisinin.

Artemisia annua

Sesquiterpene lactone

Chalcone isomerase

Flavonoid Biosynthesis

10.3389/fpls.2019.00984

Cite

Citations (48)

Mutation of theArabidopsisLON2 peroxisomal protease enhances pexophagy

Autophagy (2014)

Bonnie Bartel Lisa M. Farmer Mauro A. Rinaldi Pierce G. Young Charles Danan

Peroxisomes are critical organelles housing various, often oxidative, reactions. Pexophagy, the process by which peroxisomes are selectively targeted for destruction via autophagy, is characterized in yeast and mammals but had not been reported in plants. In this article, we describe how the peroxisome-related aberrations of a mutant defective in the LON2 peroxisomal protease are suppressed when autophagy is prevented by mutating any of several key autophagy-related (ATG) genes. Our results reveal that plant peroxisomes can be degraded by selective autophagy and suggest that pexophagy is accelerated when the LON2 protease is disabled.

Organelle

ATG8

10.4161/auto.27565

Cite

Citations (25)

The cytochrome b5 dependent C-5(6) sterol desaturase DES5A from the endoplasmic reticulum of Tetrahymena thermophila complements ergosterol biosynthesis mutants in Saccharomyces cerevisiae

Steroids (2012)

Tomás Poklépovich Mauro A. Rinaldi Mariela L. Tomazic Nicolás Octavio Favale Aaron P. Turkewitz

Ergosterol

Cytochrome b5

10.1016/j.steroids.2012.08.015

Cite

Citations (18)

The Roles of β-Oxidation and Cofactor Homeostasis in Peroxisome Distribution and Function in Arabidopsis thaliana

Genetics (2016)

Mauro A. Rinaldi Ashish Patel Jaeseok Park Ko-Eun Lee Lucia C. Strader

Abstract Key steps of essential metabolic pathways are housed in plant peroxisomes. We conducted a microscopy-based screen for anomalous distribution of peroxisomally targeted fluorescence in Arabidopsis thaliana. This screen uncovered 34 novel alleles in 15 genes affecting oil body mobilization, fatty acid β-oxidation, the glyoxylate cycle, peroxisome fission, and pexophagy. Partial loss-of-function of lipid-mobilization enzymes conferred peroxisomes clustered around retained oil bodies without other notable defects, suggesting that this microscopy-based approach was sensitive to minor perturbations, and that fatty acid β-oxidation rates in wild type are higher than required for normal growth. We recovered three mutants defective in PECTIN METHYLESTERASE31, revealing an unanticipated role in lipid mobilization for this cytosolic enzyme. Whereas mutations reducing fatty acid import had peroxisomes of wild-type size, mutations impairing fatty acid β-oxidation displayed enlarged peroxisomes, possibly caused by excess fatty acid β-oxidation intermediates in the peroxisome. Several fatty acid β-oxidation mutants also displayed defects in peroxisomal matrix protein import. Impairing fatty acid import reduced the large size of peroxisomes in a mutant defective in the PEROXISOMAL NAD+ TRANSPORTER (PXN), supporting the hypothesis that fatty acid accumulation causes pxn peroxisome enlargement. The diverse mutants isolated in this screen will aid future investigations of the roles of β-oxidation and peroxisomal cofactor homeostasis in plant development.

Glyoxysome

Peroxisomal disorder

Zellweger syndrome

Phytanic acid

10.1534/genetics.116.193169

Cite

Citations (35)

Bioproduction of Linalool From Paper Mill Waste

Frontiers in Bioengineering and Biotechnology (2022)

Mauro A. Rinaldi Shirley Tait Helen S. Toogood Nigel S. Scrutton

A key challenge in chemicals biomanufacturing is the maintenance of stable, highly productive microbial strains to enable cost-effective fermentation at scale. A "cookie-cutter" approach to microbial engineering is often used to optimize host stability and productivity. This can involve identifying potential limitations in strain characteristics followed by attempts to systematically optimize production strains by targeted engineering. Such targeted approaches however do not always lead to the desired traits. Here, we demonstrate both 'hit and miss' outcomes of targeted approaches in attempts to generate a stable Escherichia coli strain for the bioproduction of the monoterpenoid linalool, a fragrance molecule of industrial interest. First, we stabilized linalool production strains by eliminating repetitive sequences responsible for excision of pathway components in plasmid constructs that encode the pathway for linalool production. These optimized pathway constructs were then integrated within the genome of E. coli in three parts to eliminate a need for antibiotics to maintain linalool production. Additional strategies were also employed including: reduction in cytotoxicity of linalool by adaptive laboratory evolution and modification or homologous gene replacement of key bottleneck enzymes GPPS/LinS. Our study highlights that a major factor influencing linalool titres in E. coli is the stability of the genetic construct against excision or similar recombination events. Other factors, such as decreasing linalool cytotoxicity and changing pathway genes, did not lead to improvements in the stability or titres obtained. With the objective of reducing fermentation costs at scale, the use of minimal base medium containing paper mill wastewater secondary paper fiber as sole carbon source was also investigated. This involved simultaneous saccharification and fermentation using either supplemental cellulase blends or by co-expressing secretable cellulases in E. coli containing the stabilized linalool production pathway. Combined, this study has demonstrated a stable method for linalool production using an abundant and low-cost feedstock and improved production strains, providing an important proof-of-concept for chemicals production from paper mill waste streams. For scaled production, optimization will be required, using more holistic approaches that involve further rounds of microbial engineering and fermentation process development.

Bioproduction

10.3389/fbioe.2022.892896

Cite

Citations (9)

Disrupting Autophagy Restores Peroxisome Function to anArabidopsis lon2Mutant and Reveals a Role for the LON2 Protease in Peroxisomal Matrix Protein Degradation

The Plant Cell (2013)

Lisa M. Farmer Mauro A. Rinaldi Pierce G. Young Charles Danan Sarah E. Burkhart

Abstract Peroxisomes house critical metabolic reactions that are essential for seedling development. As seedlings mature, metabolic requirements change, and peroxisomal contents are remodeled. The resident peroxisomal protease LON2 is positioned to degrade obsolete or damaged peroxisomal proteins, but data supporting such a role in plants have remained elusive. Arabidopsis thaliana lon2 mutants display defects in peroxisomal metabolism and matrix protein import but appear to degrade matrix proteins normally. To elucidate LON2 functions, we executed a forward-genetic screen for lon2 suppressors, which revealed multiple mutations in key autophagy genes. Disabling core autophagy-related gene (ATG) products prevents autophagy, a process through which cytosolic constituents, including organelles, can be targeted for vacuolar degradation. We found that atg2, atg3, and atg7 mutations suppressed lon2 defects in auxin metabolism and matrix protein processing and rescued the abnormally large size and small number of lon2 peroxisomes. Moreover, analysis of lon2 atg mutants uncovered an apparent role for LON2 in matrix protein turnover. Our data suggest that LON2 facilitates matrix protein degradation during peroxisome content remodeling, provide evidence for the existence of pexophagy in plants, and indicate that peroxisome destruction via autophagy is enhanced when LON2 is absent.

Peroxisomal targeting signal

Organelle

Protein Degradation

10.1105/tpc.113.113407

Cite

Citations (118)

Alternative metabolic pathways and strategies to high-titre terpenoid production inEscherichia coli

Natural Product Reports (2021)

Mauro A. Rinaldi Clara A. Ferraz Nigel S. Scrutton

Covering: up to 2021Terpenoids are a diverse group of chemicals used in a wide range of industries. Microbial terpenoid production has the potential to displace traditional manufacturing of these compounds with renewable processes, but further titre improvements are needed to reach cost competitiveness. This review discusses strategies to increase terpenoid titres in

Metabolic Engineering

Mevalonate pathway

Metabolic pathway

10.1039/d1np00025j

Cite

Citations (60)

The PEX1 ATPase Stabilizes PEX6 and Plays Essential Roles in Peroxisome Biology

PLANT PHYSIOLOGY (2017)

Mauro A. Rinaldi Wendell A. Fleming Kim L. Gonzalez Jaeseok Park Meredith J. Ventura

A variety of metabolic pathways are sequestered in peroxisomes, conserved organelles that are essential for human and plant survival. Peroxin (PEX) proteins generate and maintain peroxisomes. The PEX1 ATPase facilitates recycling of the peroxisome matrix protein receptor PEX5 and is the most commonly affected peroxin in human peroxisome biogenesis disorders. Here, we describe the isolation and characterization of, to our knowledge, the first Arabidopsis (Arabidopsis thaliana) pex1 missense alleles: pex1-2 and pex1-3pex1-2 displayed peroxisome-related defects accompanied by reduced PEX1 and PEX6 levels. These pex1-2 defects were exacerbated by growth at high temperature and ameliorated by growth at low temperature or by PEX6 overexpression, suggesting that PEX1 enhances PEX6 stability and vice versa. pex1-3 conferred embryo lethality when homozygous, confirming that PEX1, like several other Arabidopsis peroxins, is essential for embryogenesis. pex1-3 displayed symptoms of peroxisome dysfunction when heterozygous; this semidominance is consistent with PEX1 forming a heterooligomer with PEX6 that is poisoned by pex1-3 subunits. Blocking autophagy partially rescued PEX1/pex1-3 defects, including the restoration of normal peroxisome size, suggesting that increasing peroxisome abundance can compensate for the deficiencies caused by pex1-3 and that the enlarged peroxisomes visible in PEX1/pex1-3 may represent autophagy intermediates. Overexpressing PEX1 in wild-type plants impaired growth, suggesting that excessive PEX1 can be detrimental. Our genetic, molecular, and physiological data support the heterohexamer model of PEX1-PEX6 function in plants.

10.1104/pp.17.00548

Cite

Citations (20)