Biology subjects

Langley, C.

Publications and source records attributed to Langley, C..

4 recordsLinked to original sources

bioRxiv2023

Directed evolution of piperazic acid incorporation by a nonribosomal peptide synthetase

Engineering of biosynthetic enzymes is increasingly employed to synthesize structural analogues of antibiotics. Of special interest are non-ribosomal peptide synthetases (NRPSs) responsible for production of important antimicrobial peptides. Here, directed evolution of an adenylation domain of a Pro-specific NRPS module completely switched substrate specificity to the non-standard amino acid piperazic acid (Piz) bearing a labile N-N bond. This success was achieved by LC-MS/MS based screening of small, rationally designed mutant libraries and can presumably be replicated with a larger number of substrates and NRPS modules. The evolved NRPS produces a Piz-derived gramicidin S analog. Thus, we give new impetus to the too-early dismissed idea that widely accessible low-throughput methods can switch the specificity of NRPSs in a biosynthetically useful fashion.

synthetic biology↗

bioRxiv2023

Common roles for serotonin in rats and humans for computations underlying flexible decision-making

Serotonin is critical for adapting behavior flexibly to meet changing environmental demands. Cognitive flexibility is important both for successful attainment of goals, as well as for social interactions, and is frequently impaired in neuropsychiatric disorders, including obsessive-compulsive disorder (OCD). However, a unifying mechanistic framework accounting for the role of serotonin in behavioral flexibility has remained elusive. Here, we demonstrate common effects of manipulating serotonin function across two species (rats and humans) on latent processes supporting choice behavior during probabilistic reversal learning using computational modelling. The findings support a role of serotonin in behavioral flexibility and plasticity, indicated, respectively, by increases or decreases in choice repetition ( stickiness) or reinforcement learning rates depending upon manipulations intended to increase or decrease serotonin function. More specifically, the rate at which expected value increased following reward and decreased following punishment (reward and punishment learning rates) was greatest after sub-chronic administration of the selective serotonin reuptake (SSRI) citalopram (5 mg/kg for 7 days followed by 10 mg/kg twice a day for 5 days) in rats. Conversely, humans given a single dose of an SSRI (20mg escitalopram), which can decrease post-synaptic serotonin signalling, and rats that received the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), which destroys forebrain serotonergic neurons, exhibited decreased reward learning rates. A basic perseverative tendency ( stickiness), or choice repetition irrespective of the outcome produced, was likewise increased in rats after the 12-day SSRI regimen and decreased after single dose SSRI in humans and 5,7-DHT in rats. These common effects of serotonergic manipulations on rats and humans - identified via computational modelling - suggest an evolutionarily conserved role for serotonin in plasticity and behavioral flexibility and have clinical relevance transdiagnostically for neuropsychiatric disorders.

neuroscience↗

bioRxiv2022

Expansion of the Catalytic Repertoire of Alcohol Dehydrogenases in Plant Metabolism

Medium-chain alcohol dehydrogenases (ADHs) comprise a highly conserved enzyme family that catalyse the reversible reduction of aldehydes. However, recent discoveries in plant natural product biosynthesis suggest that the catalytic repertoire of ADHs has been expanded. Here we report the crystal structure of dihydroprecondylocarpine acetate synthase (DPAS), an ADH that catalyses the non-canonical 1,4 reduction of an ,{beta}-unsaturated iminium moiety. Comparison with structures of plant-derived ADHs that catalyse 1,2-aldehyde and 1,2-iminium reductions suggest how the canonical ADH active site can be modified to carry out atypical carbonyl reductions, providing insight into how chemical reactions are diversified in plant metabolism.

biochemistry↗

bioRxiv2021

Is what you see what you get? The relationship between field observed and actual aphid parasitism rates in canola crops

BACKGROUNDEstimating parasitoid abundance in the field can be difficult, even more so when attempting to quantify parasitism rates and the ecosystem service of biological control that parasitoids can provide. To understand how observed parasitism rates (in-field mummy counts) of the green peach aphid, Myzus persicae (Sulzer) (Homoptera: Aphididae) translate to actual parasitism rates (laboratory-reared parasitoid counts), field work was undertaken in Australian canola fields over a growing season. Parasitoids were reared within a controlled laboratory setting. RESULTSTotal observed and actual parasitism rates of M. persicae varied considerably across regions, but less so on a field level. Overall, actual parasitism was on average 2.4 times higher than that observed in the field, with rates an average of 4-fold higher in South Australia. As crop growth stage progressed, the percentage of mummies observed increased. Percentage of parasitoids reared also increased with crop growth stage, averaging 3.4% during flowering and reaching 14.4% during podding/senescing. Although there was a greater diversity of reared parasitoid species at later crop growth stages, actual parasitism rate was unaffected by parasitoid species. Diaeretiella rapae was the most commonly reared parasitoid, increasing in abundance with crop growth stage. CONCLUSIONThese findings indicate that mummy counts alone do not provide a clear representation of parasitism within fields.

zoology↗