An Investigation of the Biosynthesis of Citromycetin in PenicWium frequentans using IT-and I4C-Labelled Precursors

The alternating oxygenation pattern of the carbon skeleton of these metabolites suggests a polyketide biosynthesis but the unusual branched structure cannot be derived straightforwardly from a single unbranched polyketone chain. The biosynthesis of citromycetin (1) has therefore been the subject of much speculation. Four representative proposals which have guided our planning in the present investigation are presented in Scheme 1. Pathways A and B are 'two chain pathways,'6 according to which the citromycetin skeleton might be formed by the combination of two polyketide intermediates, each formed separately from a different polyketide chain. Pathways C7 and D8 are of a more conventional type in which the skeleton might arise by modification of an intermediate derived from a single chain. The various structural types represented by intermediates (5)-(lo), are well represented among polyketide natural products, with the notable exception of compound (7), which is unusual in having its carboxy terminus as the longer of the two uncyclised residues attached to its aromatic ring.g For clarity, it is assumed in Scheme 1 that a compound such as (ll), an uncyclised analogue of (l), is formed as an intermediate

Minimal climate impacts from short-lived climate forcers following emission reductions related to the COVID-19 pandemic

We present an assessment of the impacts on atmospheric composition and radiative forcing of short-lived pollutants following worldwide decrease in anthropogenic activity and emissions comparable to what has occurred in response to the COVID-19 pandemic, using the global composition-climate model UKCA. Emission changes reduce tropospheric hydroxyl radical and ozone burdens, increasing methane lifetime. Reduced SO2 emissions and oxidising capacity lead to a decrease in sulphate aerosol and increase in aerosol size, with accompanying reductions to cloud droplet concentration. However, large reductions in black carbon emissions increase aerosol albedo. Overall, the changes in ozone and aerosol direct effects (neglecting aerosol-cloud interactions which were statistically insignificant but whose response warrants future investigation) yield a radiative forcing of -33 to -78 mWm-2. Upon cessation of emission reductions the short-lived climate forcers rapidly return to pre-COVID levels, meaning these changes are unlikely to have lasting impacts on climate assuming emissions return to pre-intervention levels

Performance of Queensland’s net-free zones

On 1 November 2015, three net-free zones (NFZs) were established in the Cairns, Mackay and Rockhampton regions. The objective of the NFZs is for recreational fishers to catch more and bigger fish, which will increase their enjoyment of recreational fishing in the region. If this occurs, fishers are likely to travel from further afield to fish NFZs, thereby supporting local businesses and tourism. To examine the impact of the NFZs on recreational fishing, surveys were undertaken at local boat ramps and tackle shops from 2015–18. These surveys examined: • if fishing effort has increased • whether important recreational fish species were larger and more commonly caught • if fishers travelled further to fish the NFZs • if recreational fishers’ satisfaction and expectations of fishing in NFZs have changed through time. The results of these surveys were compared to a combined set of reference areas (other areas in Queensland where NFZs were not introduced in November 2015) to assess the impacts of the NFZs relative to other trends in recreational fishing through time. The full benefits of NFZs on the number and size of fish caught by recreational fishers are likely to take time to emerge, however recreational fishers are now harvesting larger barred javelin in the Rockhampton NFZ compared to the reference areas, which have not changed. In 2016 and 2017 Barramundi kept by recreational fishers in the Rockhampton NFZ were also larger than the reference areas. The size or number of fish caught by recreational fishers has not increased in the Mackay or Cairns NFZs. More fishers are travelling further to fish the Rockhampton NFZ since it was created in November 2015. This is likely due to the high levels of community engagement and awareness in Rockhampton, with the council and local groups supporting and promoting the NFZ. The number of trailers counted at the boat ramps has remained steady at all NFZs and reference areas since the NFZs were implemented. Recreational fishers’ satisfaction with fishing in the NFZs is generally positive and appears to be increasing. Overall, fishing satisfaction over the previous 12 months was greater in 2018 than in 2015 or 2016. In Cairns and Rockhampton, satisfaction was similar between years, but in Mackay satisfaction was significantly greater in 2016 and 2018 than 2015. In 2018, recreational fishers in the NFZs were more satisfied with the following activities compared to 2015 and 2016: more exciting fights with fish; the number and size of fish caught; the quality of fishing in the area. Expectations varied depending on the NFZ and frequency of fishing. Interestingly, while catching a fish is important to recreational fishers, many people stated that it is not necessary for a satisfying fishing trip. Generally, the effects of NFZs have been positive for recreational fishing. The predicted flow-on benefits of NFZs (e.g. tourism) requires that fishers are satisfied with their fishing trips, which depends largely on them catching more targeted species. As NFZs age, they might produce stronger effects on recreational fishing catches, but these effects will vary between regions due to the area covered by the NFZ, environmental factors such as floods and drought, and the reproductive and migratory capabilities of the targeted fish and their prey. Monitoring the performance of NFZs will continue as part of Fisheries Queensland’s Fisheries Monitoring program

A collinear-spin machine learned interatomic potential for Fe\textsubscript{7}Cr\textsubscript{2}Ni alloy

We have developed a new machine learned interatomic potential for the prototypical austenitic steel Fe$_{7}$Cr$_{2}$Ni, using the Gaussian approximation potential (GAP) framework. This new GAP can model the alloy's properties with higher accuracy than classical interatomic potentials like embedded atom models (EAM), while also allowing us to collect much more statistics than expensive first-principles methods like density functional theory (DFT). We also extended the GAP input descriptors to approximate the effects of collinear spins (Spin GAP), and demonstrate how this extended model successfully predicts low temperature structural distortions due to the antiferromagnetic spin state. We demonstrate the application of the Spin GAP model for bulk properties and vacancies and validate against DFT. These results are a step towards modelling ageing in austenitic steels with close to DFT accuracy but at a fraction of its cost

Knowledge-based design of bimodular and trimodular polyketide synthases based on domain and module swaps: a route to simple statin analogues

AbstractBackground: Polyketides are structurally diverse natural products that have a range of medically useful activities. Nonaromatic bacterial polyketides are synthesised on modular polyketide synthase (PKS) multienzymes, in which each cycle of chain extension requires a different ‘module’ of enzymatic activities. Attempts to design and construct modular PKSs that synthesise specified novel polyketides provide a particularly stringent test of our understanding of PKS structure and function.Results: We have constructed bimodular and trimodular PKSs based on DEBS1-TE, a derivative of the erythromycin PKS that contains only modules 1 and 2 and a thioesterase (TE), by substituting multiple domains with appropriate counterparts derived from the rapamycin PKS. Hybrid PKSs were obtained that synthesised the predicted target triketide lactones, which are simple analogues of cholesterol-lowering statins. In constructing intermodular fusions, whether between modules in the same or in different proteins, it was found advantageous to preserve intact the acyl carrier protein-ketosynthase (ACP-KS) didomain that spans the junction between successive modules.Conclusions: Relatively simple considerations govern the construction of functional hybrid PKSs. Fusion sites should be chosen either in the surface-accessible linker regions between enzymatic domains, as previously revealed, or just inside the conserved margins of domains. The interaction of an ACP domain with the adjacent KS domain, whether on the same polyketide or not, is of particular importance, both through conservation of appropriate protein-protein interactions, and through optimising molecular recognition of the altered polyketide chain in the key transfer of the acyl chain from the ACP of one module to the KS of the downstream module

Collinear-spin machine learned interatomic potential for Fe7Cr2Ni alloy

We have developed a machine learned interatomic potential for the prototypical austenitic steel Fe7Cr2Ni, using the Gaussian approximation potential (GAP) framework. This GAP can model the alloy's properties with close to density functional theory (DFT) accuracy, while at the same time allowing us to access larger length and time scales than expensive first-principles methods. We also extended the GAP input descriptors to approximate the effects of collinear spins (spin GAP), and demonstrate how this extended model successfully predicts structural distortions due to antiferromagnetic and paramagnetic spin states. We demonstrate the application of the spin GAP model for bulk properties and vacancies and validate against DFT. These results are a step towards modeling the atomistic origins of ageing in austenitic steels with higher accuracy

Novel octaketide macrolides related to 6-deoxyerythronolide B provide evidence for iterative operation of the erythromycin polyketide synthase

AbstractBackground: The macrolide antibiotic erythromycin A, like other complex aliphatic polyketides, is synthesised by a bacterial modular polyketide synthase (PKS). Such PKSs, in contrast to other fatty acid and polyketide synthases which work iteratively, contain a separate set or module of enzyme activities for each successive cycle of polyketide chain extension, and the number and type of modules together determine the structure of the polyketide product. Thus, the six extension modules of the erythromycin PKS (DEBS) together catalyse the production of the specific heptaketide 6-deoxyerythronolide B.Results: A mutant strain of the erythromycin producer Saccharopolyspora erythraea, which accumulates the aglycone intermediate erythronolide B, was found unexpectedly to produce two novel octaketides, both 16-membered macrolides. These compounds were detectable in fermentation broths of wild-type S. erythraea, but not in a strain from which the DEBS genes had been specifically deleted. From their structures, both of these octaketides appear to be aberrant products of DEBS in which module 4 has ‘stuttered’, that is, has catalysed two successive cycles of chain extension.Conclusions: The isolation of novel DEBS-derived octaketides provides the first evidence that an extension module in a modular PKS has the potential to catalyse iterative rounds of chain elongation like other type I FAS and PKS systems. The factors governing the extent of such ‘stuttering’ remain to be determined

The Confederate military commissions of Edwin G. Lee, 1860-1864

Official military commissions, resignations, receipts for pay and other documents associated with the military career Edwin G. Lee. The documents include: An appointment as first lieutenant in the Virginia militia, June 1860 An appointment as a major in the active volunteer forces of Virginia, July 1861 An assignment to the 33rd Virginia Regiment, July 27, 1861 A resignation (at rank of Colonel), December 1862 A commission as Lieutenant Colonel in the 33rd Virginia Regiment, dated January 14, 1863 with term of service beginning in April of that year A certificate of nomination by the President (of the Confederate States) to Lieutenant Colonel in the Adjutant General\u27s department, Provisional Army of the Confederate States, March 13, 1863 Appointment as Major Assistant Adjutant General, Provisional Army of the Confederate States, April 11, 1863 An acceptance of resignation as acting Master in the Confederate States Navy, July 21, 1863 Appointment as Colonel of Cavalry in the Provisional Army of the Confederate States, November 19, 1863 Appointment as Brigadier General in the Provisional Army of the Confederate States, September 23, 1864 Certificate of payment to Lee, Paymaster\u27s Office, Staunton, Virginia, $544, October 31, 1864 Edwin Gray Lee also served the Confederacy in Canada during and after the war.https://digitalcommons.wofford.edu/littlejohnedwinlee/1000/thumbnail.jp