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Nature serves as a rich source of molecules with immense chemical diversity. Aptly named, these ‘natural products’ boast a wide variety of environmental, medicinal and industrial applications. Type II polyketides, in particular, confer substantial medicinal benefits, including antibacterial, antifungal, anticancer and anti-inflammatory properties. These molecules are produced by enzyme assemblies known as type II polyketide synthases (PKSs), which use domains such as the ketosynthase chain-length factor and acyl carrier protein to produce polyketides with varying lengths, cyclization patterns and oxidation states. In this work, we use a novel bioinformatic workflow to identify biosynthetic gene clusters (BGCs) that code for the core type II PKS enzymes. This method does not rely on annotation and thus was able to unearth previously ‘hidden’ type II PKS BGCs. This work led us to identify over 6000 putative type II PKS BGCs spanning a diverse set of microbial phyla, nearly double those found in most recent studies. Notably, many of these newly identified BGCs were found in non-actinobacteria, which are relatively underexplored as sources of type II polyketides. Results from this work lay an important foundation for future bioprospecting and engineering efforts that will enable sustainable access to diverse and structurally complex molecules with medicinally relevant properties. 

Abstract Background As technology moves rapidly forward and our world becomes more interconnected, we are seeing increases in the complexity and challenge associated with scientific problems. More than ever before, scientists will need to be resilient and able to cope with challenges and failures en route to success. However, we still understand relatively little about how these skills manifest in STEM contexts broadly, and how they are developed by STEM undergraduate students. While recent studies have begun to explore this area, no measures exist that are specifically designed to assess coping behaviors in STEM undergraduate contexts at scale. Fortunately, multiple measures of coping do exist and have been previously used in more general contexts. Drawing strongly from items used in the COPE and Brief COPE, we gathered a pool of items anticipated to be good measures of undergraduate students’ coping behaviors in STEM. We tested the validity of these items for use with STEM students using exploratory factor analyses, confirmatory factor analyses, and cognitive interviews. In particular, our confirmatory factor analyses and cognitive interviews explored whether the items measured coping for persons excluded due to ethnicity or race (PEERs). Results Our analyses revealed two versions of what we call the STEM-COPE instrument that accurately measure several dimensions of coping for undergraduate STEM students. One version is more fine-grained. We call this the Coping Behaviors version, since it is more specific in its description of coping actions. The other contains some specific scales and two omnibus scales that describe what we call challenge-engaging and challenge-avoiding coping. This version is designated the Coping Styles version. We confirmed that both versions can be used reliably in PEER and non-PEER populations. Conclusions The final products of our work are two versions of the STEM-COPE. Each version measures several dimensions of coping that can be used in individual classrooms or across contexts to assess STEM undergraduate students’ coping with challenges or failures. Each version can be used as a whole, or individual scales can be adopted and used for more specific studies. This work also highlights the need to either develop or adapt other existing measures for use with undergraduate STEM students, and more specifically, for use with sub-populations within STEM who have been historically marginalized or minoritized. 

Abstract Background The ability to navigate obstacles and embrace iteration following failure is a hallmark of a scientific disposition and is hypothesized to increase students’ persistence in science, technology, engineering, and mathematics (STEM). However, this ability is often not explicitly explored or addressed by STEM instructors. Recent collective interest brought together STEM instructors, psychologists, and education researchers through the National Science Foundation (NSF) research collaborative Factors affecting Learning, Attitudes, and Mindsets in Education network (FLAMEnet) to investigate intrapersonal elements (e.g., individual differences, affect, motivation) that may influence students’ STEM persistence. One such element is fear of failure (FF), a complex interplay of emotion and cognition occurring when a student believes they may not be able to meet the needs of an achievement context. A validated measure for assessing FF, the Performance Failure Appraisal Inventory (PFAI) exists in the psychological literature. However, this measure was validated in community, athletic, and general undergraduate samples, which may not accurately reflect the motivations, experiences, and diversity of undergraduate STEM students. Given the potential role of FF in STEM student persistence and motivation, we felt it important to determine if this measure accurately assessed FF for STEM undergraduates, and if not, how we could improve upon or adapt it for this purpose. Results Using exploratory and confirmatory factor analysis and cognitive interviews, we re-validated the PFAI with a sample of undergraduates enrolled in STEM courses, primarily introductory biology and chemistry. Results indicate that a modified 15-item four-factor structure is more appropriate for assessing levels of FF in STEM students, particularly among those from groups underrepresented in STEM. Conclusions In addition to presenting an alternate factor structure, our data suggest that using the original form of the PFAI measure may significantly misrepresent levels of FF in the STEM context. This paper details our collaborative validation process and discusses implications of the results for choosing, using, and interpreting psychological assessment tools within STEM undergraduate populations. 

Abstract Phosphopantetheinyl transferases (PPTases) play an essential role in primary and secondary metabolism. These enzymes facilitate the post-translational activation of acyl carrier proteins (ACPs) central to the biosynthesis of fatty acids and polyketides. Modulation of ACP-PPTase interactions is a promising approach to both increase access to desired molecular outputs and disrupt mechanisms associated with disease progression. However, such an approach requires understanding the molecular principles that govern ACP-PPTase interactions across diverse synthases. Through a multi-year, course-based undergraduate research experience (CURE), 17 ACPs representing a range of putative type II polyketide synthases, from actinobacterial and non-actinobacterial phyla, were evaluated as substrates for three PPTases (AcpS, Sfp, and vulPPT). The observed PPTase compatibility, sequence-level analyses, and predictive structural modelling suggest that ACP selectivity is driven by amino acids surrounding the conserved, modified serine on the ACP. We propose that vulPPT and Sfp are driven primarily by hydrophobic contacts, whereas AcpS may favor ACPs which exhibit high net-negative charge density, as well as a broad electronegative surface distribution. Furthermore, we report a plausible, hitherto unreported hydrophobic interaction between vulPPT and a conserved ACP crease, upstream of the invariant serine, which may facilitate docking. This work provides a catalog of compatible and incompatible ACP-PPTase partnerships, highlighting specific regions on the ACP and/or PPTase that show promise for future strategic engineering and inhibitor development efforts.