Fundamental features of microbial cellulose utilization are examined at successively higher levels of aggregation encompassing the structure and composition of cellulosic biomass, taxonomic diversity, cellulase enzyme systems, molecular biology of cellulase enzymes, physiology of cellulolytic microorganisms, ecological aspects of cellulase-degrading communities, and rate-limiting factors in nature. The methodological basis for studying microbial cellulose utilization is considered relative to quantification of cells and enzymes in the presence of solid substrates as well as apparatus and analysis for cellulose-grown continuous cultures. Quantitative description of cellulose hydrolysis is addressed with respect to adsorption of cellulase enzymes, rates of enzymatic hydrolysis, bioenergetics of microbial cellulose utilization, kinetics of microbial cellulose utilization, and contrasting features compared to soluble substrate kinetics. A biological perspective on processing cellulosic biomass is presented, including features of pretreated substrates and alternative process configurations. Organism development is considered for "consolidated bioprocessing" (CBP), in which the production of cellulolytic enzymes, hydrolysis of biomass, and fermentation of resulting sugars to desired products occur in one step. Two organism development strategies for CBP are examined: (i) improve product yield and tolerance in microorganisms able to utilize cellulose, or (ii) express a heterologous system for cellulose hydrolysis and utilization in microorganisms that exhibit high product yield and tolerance. A concluding discussion identifies unresolved issues pertaining to microbial cellulose utilization, suggests approaches by which such issues might be resolved, and contrasts a microbially oriented cellulose hydrolysis paradigm to the more conventional enzymatically oriented paradigm in both fundamental and applied contexts.

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Microbial cellulose utilization: fundamentals and biotechnology.

Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory.

Origins and Evolution of Antibiotic Resistance

SUMMARY A collection of 267 strains, representing many of the principal biotypes among aerobic pseudomonads, has been subjected to detailed study, with particular emphasis on biochemical, physiological and nutritional characters. A total of 146 different organic compounds were tested for their ability to serve as sources of carbon and energy. Other characters that were studied included : production of extracellular hydrolases; nitrogen sources and growth factor requirements H-chemolithotrophy; denitrifying ability; pigment production; ability to accumulate poly-p-hydroxybutyrate as a cellular reserve material; biochemical mechanisms of aromatic ring cleavage; and nature of the aerobic electron transport system. The resultant data have revealed many hitherto unrecognized characters of taxonomic significance. As a consequence, it has become possible to recognize among the biotypes examined a limited number of species which can be readily and clearly distinguished from one another by multiple, unrelated phenotypic differences.

The Aerobic Pseudomonads a Taxonomic Study

The short history, specific features and future prospects of research of microbial metabolites, including antibiotics and other bioactive metabolites, are summarized. The microbial origin, diversity of producing species, functions and various bioactivities of metabolites, unique features of their chemical structures are discussed, mainly on the basis of statistical data. The possible numbers of metabolites may be discovered in the future, the problems of dereplication of newly isolated compounds as well as the new trends and prospects of the research are also discussed.

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Bioactive microbial metabolites.

The use of fossil fuels is now widely accepted as unsustainable due to depleting resources and the accumulation of greenhouse gases in the environment that have already exceeded the “dangerously high” threshold of 450 ppm CO2-e. To achieve environmental and economic sustainability, fuel production processes are required that are not only renewable, but also capable of sequestering atmospheric CO2. Currently, nearly all renewable energy sources (e.g. hydroelectric, solar, wind, tidal, geothermal) target the electricity market, while fuels make up a much larger share of the global energy demand (∼66%). Biofuels are therefore rapidly being developed. Second generation microalgal systems have the advantage that they can produce a wide range of feedstocks for the production of biodiesel, bioethanol, biomethane and biohydrogen. Biodiesel is currently produced from oil synthesized by conventional fuel crops that harvest the sun’s energy and store it as chemical energy. This presents a route for renewable and carbon-neutral fuel production. However, current supplies from oil crops and animal fats account for only approximately 0.3% of the current demand for transport fuels. Increasing biofuel production on arable land could have severe consequences for global food supply. In contrast, producing biodiesel from algae is widely regarded as one of the most efficient ways of generating biofuels and also appears to represent the only current renewable source of oil that could meet the global demand for transport fuels. The main advantages of second generation microalgal systems are that they: (1) Have a higher photon conversion efficiency (as evidenced by increased biomass yields per hectare): (2) Can be harvested batch-wise nearly all-year-round, providing a reliable and continuous supply of oil: (3) Can utilize salt and waste water streams, thereby greatly reducing freshwater use: (4) Can couple CO2-neutral fuel production with CO2 sequestration: (5) Produce non-toxic and highly biodegradable biofuels. Current limitations exist mainly in the harvesting process and in the supply of CO2 for high efficiency production. This review provides a brief overview of second generation biodiesel production systems using microalgae.

https://www.springer.com/cda/content/document/cda_downloaddocument/BioEnergyResearch_Second+Generation+Biofuels+High-Efficiency+Microalgae+for+Biodiesel+Production.pdf?SGWID=0-0-45-1347846-0

Second generation biofuels: high-efficiency microalgae for biodiesel production

Carbohydrate utilization by clostridium thermocellum : importance of internal pH in regulating growth

The previously reported inability of methionine to stimulate cephalosporin C production in a cysteine auxotroph is due to cysteine interference with methionine uptake. In such a cse, "illicit transport" of alanylmethionine can be used to demonstrate the efficacy of methionine in such mutants blocked in the path from methionine to cysteine. This result supports the hypothesis that the stimulatory activity of methionine is not due to its ability to donate sulfur to the caphalosporin C molecule.

Stimulation of cephalosporin production by methionine peptides in a mutant blocked in reverse transsulfuration.

The hydroxylase in cell-free extracts of Actinomadura sp strain 2966 converts compactin to pravastatin. It requires NADPH as coenzyme and Mg2+ as cofactor; Mn2+ can partially replace Mg2+. In contrast with the inducible cytochrome P-450 system of Streptomyces carbophilus which catalyzes the same overall reaction, this constitutive hydroxylase is stimulated by ATP and ascorbic acid and is not inactivated by CO.

A new hydroxylase system in Actinomadura sp cells converting compactin to pravastatin

My professional life has been devoted to the study of microbial products and their biosynthesis, regulation, and overproduction These have included primary metabolites (glutamic acid, tryptophan, inosinic acid, guanylic acid, vitamin B(12), riboflavin, pantothenic acid, ethanol, and lactic acid) and secondary metabolites (penicillin, cephalosporins, streptomycin, fosfomycin, gramicidin S, rapamycin, indolmycin, microcin B17, fumagillin, mycotoxins, Monascus pigments, and tetramethylpyrazine) Other areas included microbial nutrition, strain improvement, bioconversions of statins and beta-lactams, sporulation and germination, plasmid stability, gel microdroplets, and the production of double-stranded RNA, the polymer xanthan, and enzymes (polygalacturonase, protease, cellulase) Most of the studies were carried out with me by devoted and hardworking industrial scientists for 15 years at Merck & Co and by similarly characterized students, postdoctorals, and visiting scientists during my 32 years at the Massachusetts Institute of Technology I owe much of my success to my mentors from academia and industry My recent research activities with undergraduate students at the Charles A Dana Research Institute for Scientists Emeriti (RISE) at Drew University have been very rewarding and are allowing me to continue my career

Pickles, Pectin, and Penicillin

Platensimycin and platencin are novel antibiotics produced by Streptomyces platensis. They are potent and non-toxic natural products active against Gram-positive pathogens, including antibiotic-resistant strains and Mycobacterium tuberculosis. They were isolated using an intriguing target-based whole-cell antisense differential sensitivity assay as inhibitors of fatty acid biosynthesis of type II. This type of biosynthesis is not present in humans. Platensimycin inhibits the elongation-condensing enzyme FabF, whereas platencin inhibits both FabF and FabH. For these antibiotics to become successful drugs, their pharmacokinetics must be improved. They have too high a rate of clearance in the body, yielding a low degree of systematic exposure. They work well when administered by continuous infusion, but this is not a useful method of delivery to patients. The two antibiotics and many analogs have been prepared by chemical synthesis. Natural congeners have also been obtained from the producing actinomycete. However, none of these molecules are as active as platensimycin and platencin. Using tools of rational metabolic engineering, superior strains have been produced making hundreds of times more antibiotic than the natural strains.

Arnold L. Demain

Papers

Carbohydrate utilization by clostridium thermocellum : importance of internal pH in regulating growth

Stimulation of cephalosporin production by methionine peptides in a mutant blocked in reverse transsulfuration.

A new hydroxylase system in Actinomadura sp cells converting compactin to pravastatin

Pickles, Pectin, and Penicillin

Platensimycin and Platencin: Promising Antibiotics for Future Application in Human Medicine