Deposits of clastic carbonate-dominated (calciclastic) sedimentary slope systems in the rock record have been identified mostly as linearly-consistent carbonate apron deposits, even though most ancient clastic carbonate slope deposits fit the submarine fan systems better. Calciclastic submarine fans are consequently rarely described and are poorly understood. Subsequently, very little is known especially in mud-dominated calciclastic submarine fan systems. Presented in this study are a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) that reveals a >250 m thick calciturbidite complex deposited in a calciclastic submarine fan setting. Seven facies are recognised from core and thin section characterisation and are grouped into three carbonate turbidite sequences. They include: 1) Calciturbidites, comprising mostly of highto low-density, wavy-laminated bioclast-rich facies; 2) low-density densite mudstones which are characterised by planar laminated and unlaminated muddominated facies; and 3) Calcidebrites which are muddy or hyper-concentrated debrisflow deposits occurring as poorly-sorted, chaotic, mud-supported floatstones. These

Phd by thesis

https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

DNA topoisomerases and their poisoning by anticancer and antibacterial drugs.

biotics of the penicillin and cephalosporin families, 3,4 as well as the glycopeptides of the vancomycin family 5 (Figure 1a). * To whom correspondence should be addressed: christopher_walsh@ hms.harvard.edu. † Harvard Medical School. ‡ Harvard University. Christopher T. Walsh is the Hamilton Kuhn Professor of Biological Chemistry and Molecular Pharmacology (BCMP) at Harvard Medical School. He has had extensive experience in academic administration, including Chairmanship of the MIT Chemistry Department (1982−1987) and the HMS Biological Chemistry & Molecular Pharmacology Department (1987−1995) as well as serving as President and CEO of the Dana Farber Cancer Institute (1992−1995). His research has focused on enzymes and enzyme inhibitors, with recent specialization on antibiotics. He and his group have authored over 590 research papers, a text (Enzymatic Reaction Mechanisms), and two books (Antibiotics: Origins, Actions, Resistance and Posttranslational Modification of Proteins: Expanding Nature’s Inventory). He is a member of the National Academy of Sciences, the Institute of Medicine, and the American Philosophical Society.

Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics: logic, machinery, and mechanisms.

Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort.

Challenges of Antibacterial Discovery

Tryptophan Aminopeptidase Activity of Several Indole Prenyltransferases from Aspergillus fumigatus

Coupling of cyclo-l-Trp-l-Trp with Hypoxanthine Increases the Structure Diversity of Guanitrypmycins

Non-ribosomal peptide synthetases (NRPSs) are key enzymes in microorganisms for the assembly of peptide backbones of biologically and pharmacologically active natural products. The monomodular NRPS-like enzymes comprise often an adenylation (A), a thiolation (T), and a thioesterase (TE) domain. In contrast to the NRPSs, they do not contain any condensation domain and usually catalyze a dimerization of α-keto carboxylic acids and thereby provide diverse scaffolds for further modifications. In this study, we established an expression system for NRPS-like genes in Saccharomyces cerevisiae. By expression of four known genes from Aspergillus terreus, their predicted function was confirmed and product yields of up to 35 mg per liter culture were achieved. Furthermore, expression of ATEG_03090 from the same fungus, encoding for the last uncharacterized NRPS-like enzyme with an A-T-TE domain structure, led to the formation of the benzoquinone derivative atromentin. All the accumulated products were isolated and their structures were elucidated by NMR and MS analyses. This study provides a convenient system for proof of gene function as well as a basis for synthetic biology, since additional genes encoding modification enzymes can be introduced.

Production of α-keto carboxylic acid dimers in yeast by overexpression of NRPS-like genes from Aspergillus terreus.

Clavicipitaceous fungi producing ergot alkaloids were recently discovered to be epibiotically associated with peltate glandular trichomes of Ipomoea asarifolia and Turbina corymbosa, dicotyledonous plants of the family Convolvulaceae. Mediators of the close association between fungi and trichomes may be sesquiterpenes, main components in the volatile oil of different convolvulaceous plants. Molecular biological studies and microscopic investigations led to the observation that the trichomes do not only secrete sesquiterpenes and palmitic acid but also seem to absorb ergot alkaloids from the epibiotic fungal species of the genus Periglandula. Thus, the trichomes are likely to have a dual and key function in a metabolic dialogue between fungus and host plant.

The key role of peltate glandular trichomes in symbiota comprising clavicipitaceous fungi of the genus periglandula and their host plants.

A dimethylallyl diphosphate:4-hydroxyphenylpyruvate dimethylallyl transferase from the novobiocin producer Streptomyces spheroides DSM 40292 was identified, partially purified and characterized. The enzyme was soluble, and specific for 4-hydroxyphenylpyruvate and dimethylallyl diphosphate as substrates. It is most likely involved in the biosynthesis of the prenylated 4-hydroxybenzoate moiety of the aminocoumarin antibiotic novobiocin.

Shu-Ming Li

Papers

Tryptophan Aminopeptidase Activity of Several Indole Prenyltransferases from Aspergillus fumigatus

Coupling of cyclo-l-Trp-l-Trp with Hypoxanthine Increases the Structure Diversity of Guanitrypmycins

Production of α-keto carboxylic acid dimers in yeast by overexpression of NRPS-like genes from Aspergillus terreus.

The key role of peltate glandular trichomes in symbiota comprising clavicipitaceous fungi of the genus periglandula and their host plants.

Novobiocin biosynthesis in Streptomyces spheroides: Identification of a dimethylallyl diphosphate: 4-Hydroxyphenylpyruvate dimethylallyl transferase