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1.
Subst Use Misuse ; 59(4): 510-519, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38037842

RESUMEN

Background: Substance use disorders (SUDs) negatively impact veterans and their relationships with others. Although there are several evidence-based treatments for SUD symptoms, there is less research on whether reduction in SUD symptoms coincides with reduction in interpersonal difficulties. Methods: In this study we examined the relationship between SUD and relationships in a national sample of 458 veterans who received approximately 12 sessions of Cognitive Behavioral Therapy for Substance Use Disorders (CBT-SUD) through the Veterans Health Administration (VHA). Results: Parallel latent growth curve modeling (LGCM) indicated that self-reported alcohol use, drug use, and interpersonal difficulties decreased over the course of treatment. Alcohol and drug use were positively associated with each other and with interpersonal difficulties at each time point, and baseline alcohol and drug use were negatively associated with the reduction of use over time. However, there was little evidence that reductions in substance use led to a reduction in interpersonal difficulties (or vice-versa). Conclusions: Findings highlight promising strategies to further understand how CBT-SUD may enhance reductions in substance use as well as improve relationships with family and friends.


Asunto(s)
Terapia Cognitivo-Conductual , Trastornos Relacionados con Sustancias , Veteranos , Humanos , Veteranos/psicología , Trastornos Relacionados con Sustancias/terapia , Trastornos Relacionados con Sustancias/psicología
2.
Contemp Clin Trials ; 126: 107096, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36693589

RESUMEN

BACKGROUND: Chronic pain and opioid use disorder (OUD) individually represent a risk to health and well-being. Concerningly, there is evidence that they are frequently co-morbid. While few treatments exist that simultaneously target both conditions, preliminary work has supported the feasibility of an integrated behavioral treatment targeting pain interference and opioid misuse. This treatment combined Acceptance and Commitment Therapy (ACT) and Mindfulness-Based Relapse Prevention (ACT+MBRP). This paper describes the protocol for the adequately powered efficacy study of this integrated treatment. METHODS: A multisite randomized controlled trial will examine the efficacy of ACT+MBRP in comparison to a parallel education control condition, focusing on opioid safety and pain education. Participants include veterans (n = 160; 21-75 years old) recruited from three Veterans Administration (VA) Healthcare Systems with chronic pain who are on a stable dose of buprenorphine. Both conditions include twelve weekly 90 min group sessions delivered via telehealth. Primary outcomes include pain interference (Patient Reported Outcome Measurement Information System - Pain Interference) and hazardous opioid use (Current Opioid Misuse Measure), which will be examined at the end of the active treatment phase and through 12 months post-intervention. Secondary analyses will evaluate outcomes including pain intensity, depression, pain-related fear, and substance use, as well as treatment mechanisms. CONCLUSION: This study will determine the efficacy of an integrated behavioral treatment program for pain interference and hazardous opioid use among veterans with chronic pain and OUD who are prescribed buprenorphine, addressing a critical need for more integrated treatments for chronic pain and OUD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04648228.


Asunto(s)
Terapia de Aceptación y Compromiso , Buprenorfina , Dolor Crónico , Trastornos Relacionados con Opioides , Veteranos , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Analgésicos Opioides/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Buprenorfina/uso terapéutico
3.
Addict Behav ; 139: 107589, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36565531

RESUMEN

BACKGROUND: Craving is a distressing symptom of opioid use disorder (OUD) that can be alleviated with medications for OUD (MOUD). Buprenorphine is an effective MOUD that may suppress craving; however, treatment discontinuation and resumed opioid use is common during the early phases of treatment. More information on the craving response through the high-risk period of initiating buprenorphine may provide meaningful information on how to better target craving, which in turn may enhance outcomes. This systematic review investigated buprenorphine doses and formulations on craving during the induction and maintenance phases of treatment, and for context also compared the craving response to other MOUD (i.e., methadone, extended-release naltrexone [XR-NTX]). METHODS: PubMed, PsycInfo, Embase, and Cochrane Central databases were searched for randomized trials of buprenorphine versus placebo, various buprenorphine formulations/doses, or other MOUD that included a measure of opioid craving. RESULTS: A total of 10 studies were selected for inclusion. Buprenorphine and buprenorphine/naloxone (BUP/NAL) were each associated with lower craving than placebo over time. Craving was greater among those prescribed lower versus higher buprenorphine doses. In comparison to other MOUD, buprenorphine or BUP/NAL was linked to greater craving than methadone in 3 of the 6 studies. BUP/NAL was associated with greater reported craving than XR-NTX. DISCUSSION: Craving is reduced over time with buprenorphine and BUP/NAL, although other MOUD may provide greater reductions in craving. Although there is currently considerable variability in the measurement of craving, it may be a valuable concept to address with individuals receiving MOUD, especially early in treatment.


Asunto(s)
Buprenorfina , Trastornos Relacionados con Opioides , Humanos , Buprenorfina/uso terapéutico , Analgésicos Opioides/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Ansia , Preparaciones de Acción Retardada , Ensayos Clínicos Controlados Aleatorios como Asunto , Trastornos Relacionados con Opioides/tratamiento farmacológico , Naltrexona/uso terapéutico , Combinación Buprenorfina y Naloxona/uso terapéutico , Metadona/uso terapéutico
4.
Surgery ; 172(6): 1673-1681, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36283843

RESUMEN

BACKGROUND: High-risk alcohol use is a common surgical risk factor. Stopping or reducing alcohol use in the weeks before and after surgery could improve surgical health and outcomes. The purpose of this study was to evaluate the feasibility and acceptability of 2 interventions that address high-risk alcohol use in the context of surgery. METHODS: Participants included patients scheduled for elective surgeries at an academic health system in the Midwestern United States. Recruitment took place by phone and text. Participants were included if they were 18 to 75 years old, scheduled for elective surgeries, and scored ≥5 on the Alcohol Use Disorders Identification Test-Consumption Tool. Participants were randomized to either a low-intensity intervention, brief advice (10-minute phone-based psychoeducation plus feedback session), or a higher-intensity intervention, health coaching (two 45-minute sessions including education, feedback, motivational interviewing, and goal setting). Assessments took place at baseline and at 1-month and 4-month follow-ups. Alcohol biomarkers were collected the day of surgery. RESULTS: The final study sample included (n = 51) participants randomized to brief advice and health coaching conditions. Participants in both conditions rated interventions as satisfactory and personally relevant. Trial retention was high (86.3%) at 4 months. Attrition was significantly higher in brief advice (n = 6) relative to health coaching (n = 1). Average weekly alcohol use decreased 50% to 60% between baseline and follow-ups in both conditions. Biomarkers corroborated self-report. CONCLUSION: The trial demonstrated intervention feasibility and acceptability. Alcohol use changed in expected directions. The next steps include a randomized controlled trial to test intervention efficacy in reducing alcohol use and surgical complications.


Asunto(s)
Alcoholismo , Entrevista Motivacional , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Proyectos Piloto , Consumo de Bebidas Alcohólicas/prevención & control , Entrevista Motivacional/métodos , Procedimientos Quirúrgicos Electivos
5.
Addict Behav ; 120: 106953, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34022757

RESUMEN

BACKGROUND: Patients in methadone maintenance treatment (MMT) with problem gambling (PG) experience worse psychosocial outcomes than their non-PG counterparts. Interventions targeting PG in MMT may enhance psychosocial functioning beyond gambling reduction and abstinence. The present study was a secondary data analysis that examined the trajectories of non-gambling outcomes of three brief PG interventions (i.e., brief psychoeducation, brief advice, motivational enhancement therapy plus cognitive-behavioral therapy [MET + CBT]) among MMT patients. METHODS: Participants (N = 109) were engaged in substance use disorder treatment, met criteria for PG, and had a current or lifetime history of MMT. Latent growth curve models examined outcome trajectories of psychiatric, medical, legal, employment, and social problems, as well as psychological distress and quality of life. Follow-up analyses examined clinically significant change. RESULTS: MET + CBT patients reported lower medical problems at baseline and over time than the brief interventions. There was no evidence of differences between interventions on the other outcomes. Psychiatric problems and psychological distress decreased over time for the entire sample, regardless of the PG intervention. About 24% and 13% of the sample demonstrated clinically significant improvements in psychological distress from baseline to 5 months, and 5 months to 12 months, respectively. Nearly 21% of the sample showed clinically significant improvements in psychiatric problems from 5 months to 12 months. Among all patients, men and those with more severe opioid dependence symptoms demonstrated the greatest psychological improvements. CONCLUSIONS: Many patients in MMT with PG experience improvements in psychological problems, including long-term improvement, regardless of the PG intervention offered.


Asunto(s)
Juego de Azar , Entrevista Motivacional , Intervención en la Crisis (Psiquiatría) , Humanos , Masculino , Metadona/uso terapéutico , Calidad de Vida
6.
Cognit Ther Res ; 45(1): 74-89, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33776170

RESUMEN

BACKGROUND: Social anxiety (SA) and depression are prevalent, often comorbid disorders, associated with poor psychosocial functioning. Experimental psychopathology approaches can clarify the transdiagnostic mechanisms underlying these disorders, but most laboratory tasks are limited. We developed and validated the Audio-Dialogue Inductions of Social Stress (A-DISS) experimental task to model real-time rejection sensitivity in a realistic and developmentally relevant context. Participants are asked to imagine overhearing peers at a party talking badly about them (Rejection) or a teacher at their school (Neutral). METHODS: Study 1 focused on identifying and refining stimuli that elicited relevant emotional responses for Rejection (e.g., increased anxiety) and Neutral (e.g., no emotional changes) conditions (N=48). Study 2 examined whether participants' SA and depression symptoms moderated the effects of A-DISS condition (N=52). RESULTS: The Rejection condition elicited higher negative affect/lower positive affect while the Neutral condition sustained stable affect. Findings were consistent across gender and race/ethnicity. Moderation analyses were statistically significant; participants with elevated SA or depression reported feeling more rejected, insecure, and anxious after Rejection than those with below average symptoms. CONCLUSIONS: Findings provide preliminary validation of a novel peer rejection task for research on understanding the affective experience of real-time rejection overall, especially for those with elevated SA and depression. SA and depression symptoms each uniquely moderating the effects of Rejection exposure on similar affective states, suggests individuals with SA or depression may benefit from interventions targeting specific reactions to rejection/stress and transdiagnostic risk factors.

7.
Drug Alcohol Depend ; 221: 108635, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33631551

RESUMEN

BACKGROUND: Cognitive functioning refers to storage and manipulation of information and includes executive functioning (EF) and attention (ATT). While physical activity (PA) improves cognitive functioning, decrements are associated with frequent substance use. This study examined PA on cognitive functioning within the context of past-year substance use. METHODS: Using NESARC-III data (N = 36,309), cross-sectional analysis examined interactions between self-reported past-year PA and substance use in relation to cognitive functioning. RESULTS: As hypothesized, light-to-moderate, vigorous, and total PA conditional main effects were positively associated with both facets of cognition, while frequent substance use conditional main effects were negatively associated with ATT and EF. The positive association between PA and cognition was diminished by substance use. Frequent binge drinking, marijuana, cocaine, and opioid use weakened the impact of light-to-moderate PA on EF, and only frequent cocaine use lessened the relationship between vigorous PA on EF. When PA intensities were combined, frequent binge drinking and cocaine use weakened the PA and EF association. Infrequent stimulant use reduced the association between all levels of PA and ATT, while infrequent marijuana use unexpectedly enhanced the relation between vigorous PA and ATT. CONCLUSIONS: Overall, PA enhanced two facets of cognitive functioning across six substances. However, these benefits are reduced in the context of frequency of substance use. The positive association between light-to-moderate PA and EF appears to be more sensitive in the context of frequent substance use than vigorous PA. Implications for public health messaging and PA as cognitive remediation treatment for substance use disorders are discussed.


Asunto(s)
Cognición , Ejercicio Físico/psicología , Conductas Relacionadas con la Salud/efectos de los fármacos , Trastornos Relacionados con Sustancias/psicología , Adolescente , Adulto , Anciano , Atención/efectos de los fármacos , Estudios Transversales , Función Ejecutiva/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autoinforme , Adulto Joven
8.
Addiction ; 116(9): 2387-2397, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33405304

RESUMEN

BACKGROUND AND AIMS: Opioid use and chronic pain are prevalent in the veteran population. Collaborative care enhances coordination between patients and their care teams, and motivational interviewing (MI) is a communication style designed to facilitate behavior change. This study evaluated the use of collaborative care with MI (CCMI) with patients with chronic pain and high-risk prescription opioid use. DESIGN: Small pilot study of a randomized controlled trial. SETTING: An urban Veterans Affairs (VA) Medical Center in the United States. PARTICIPANTS: One hundred adult veterans with chronic pain currently enrolled into primary care and receiving long-term opioid therapy. INTERVENTION AND COMPARATOR: During an initial 1-hour visit with a study primary-care physician (PCP), all veterans (n = 100) developed a personalized pain care plan, after which they were randomized to receive four sessions (at 4, 6, 8 and 12 weeks) of either CCMI (n = 51) or attention control psychoeducation (ACP; n = 49). Subsequently, participants had 30-minute follow-up visits with study PCPs and post-treatment assessment at 12 weeks. MEASUREMENTS: Co-primary outcomes measures assessed opioid risk and pain interference; secondary measures assessed pain severity, PCP rating of opioid risk and pain management goals. FINDINGS: At 12 weeks, intent-to-treat (ITT) analyses using multivariate mixed-effects linear regression were inconclusive regarding the between-group differences in primary and secondary outcomes at post-intervention (12 weeks). Bayes factors for opioid risk, pain interference, pain severity and PCP ratings were 1.96, 1.36, 0.45 and 0.82, respectively. Veterans in the CCMI group reported implementing more complementary integrative health (CIH) goals (e.g. yoga) than did those in the ACP group (d = 0.54). CONCLUSIONS: US veterans with chronic pain who received collaborative care with motivational interviewing reduced their high-risk opioid use and showed improved pain interference and severity after an intake with a primary-care provider involving shared decision-making and the creation of a personalized pain care plan.


Asunto(s)
Analgésicos Opioides , Entrevista Motivacional , Adulto , Analgésicos Opioides/uso terapéutico , Teorema de Bayes , Humanos , Manejo del Dolor , Proyectos Piloto , Estados Unidos
9.
Behav Ther ; 50(1): 50-59, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30661566

RESUMEN

Social anxiety disorder (SAD) is associated with increased risk of developing an alcohol use disorder (AUD). Most of the current literature has focused on the role of acute stress responding in this relation; however, both SAD and AUDs also are linked to insomnia symptoms (i.e., difficulty falling or staying asleep). As adolescence is a sensitive period for the onset of these disorders, the present study examined if insomnia symptoms might partially account for the SAD-AUD link in a large sample of adolescents. Data from the National Comorbidity Survey-Adolescent Supplement were examined. Participants (N = 10,140) completed interviews to assess past 12-month SAD and AUD diagnostic status as well as insomnia symptoms. Analyses tested whether insomnia symptoms accounted for a significant proportion of the SAD-AUD relation. Results indicated that insomnia symptoms were positively related to both SAD and AUD status, and the relation between SAD and AUD status was significantly reduced when insomnia symptoms were included in the model. Findings remained significant after controlling for the effects of age, gender, posttraumatic stress disorder, major depressive disorder, and other drug dependence status. Experimental examination and intensive longitudinal assessment of these relationships are needed before strong conclusions can be inferred about causality and temporal relationships. The current findings do indicate insomnia may be an important indirect and stigma-free treatment target to address in prevention and treatment efforts for SAD, AUDs, and their co-occurrence.


Asunto(s)
Alcoholismo/epidemiología , Alcoholismo/psicología , Fobia Social/epidemiología , Fobia Social/psicología , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Adolescente , Conducta del Adolescente/psicología , Adulto , Alcoholismo/diagnóstico , Comorbilidad , Femenino , Humanos , Masculino , Fobia Social/diagnóstico , Trastornos del Inicio y del Mantenimiento del Sueño/diagnóstico , Encuestas y Cuestionarios , Estados Unidos/epidemiología
10.
Exp Clin Psychopharmacol ; 27(1): 64-77, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30080059

RESUMEN

Given the high rates of relapse among patients with opioid use disorder (OUD), it is crucial to identify modifiable risk factors for negative treatment outcomes. Anxiety sensitivity (AS) is 1 such risk factor that may be associated with negative OUD treatment outcomes. The present study examined the potential impact of AS on the withdrawal process, subsequent treatment engagement, and relapse among individuals with OUD. Adults undergoing inpatient detoxification (N = 90) completed self-report and researcher-administered questionnaires on Day 4 of a 5-day buprenorphine-assisted detoxification protocol, and 1 month later a follow-up evaluation assessed treatment engagement and relapse. Although 68% of the sample engaged in subsequent treatment, 76% demonstrated poor adherence. Over half the sample (57%) reported opioid relapse 1 month later. Results revealed that greater AS and younger age predicted greater fear of withdrawal during detoxification. Contrary to the research hypotheses, AS was not a significant predictor of other treatment outcomes; rather, fear of withdrawal and prior number of opioid detoxifications predicted greater subjective withdrawal severity. During detoxification, younger age was related to greater cravings, and being a male was associated with a higher likelihood of receiving prescription anxiolytics. Following detoxification treatment, referral to residential treatment predicted greater treatment engagement, whereas greater opioid craving, number of days in an uncontrolled environment, and any nonopioid substance use postdischarge predicted greater opioid relapse. Failure to find a relationship between AS and the withdrawal process is potentially a function of the buprenorphine protocol. Overall, findings may have important implications for the treatment of OUD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Asunto(s)
Ansiolíticos/administración & dosificación , Ansiedad , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides , Síndrome de Abstinencia a Sustancias , Adulto , Factores de Edad , Analgésicos Opioides/farmacología , Ansiedad/tratamiento farmacológico , Ansiedad/psicología , Buprenorfina/uso terapéutico , Ansia/efectos de los fármacos , Femenino , Humanos , Masculino , Antagonistas de Narcóticos/farmacología , Tratamiento de Sustitución de Opiáceos/métodos , Tratamiento de Sustitución de Opiáceos/psicología , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/psicología , Factores de Riesgo , Prevención Secundaria , Factores Sexuales , Síndrome de Abstinencia a Sustancias/prevención & control , Síndrome de Abstinencia a Sustancias/psicología , Insuficiencia del Tratamiento , Adulto Joven
11.
Sports Med ; 48(3): 507-512, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29198023

RESUMEN

The use of stimulants as a treatment for attention-deficit/hyperactivity disorder (ADHD) among elite athletes is a controversial area with some arguing that stimulant use should not be permitted because it offers an advantage to athletes (fair play perspective). Guided by an integrated model of athletic performance, we address common concerns raised about stimulant use in sports from our perspective, which we coined the "performance and health perspective," highlighting relevant research and pointing to gaps in empirical research that should be addressed before bans on use of stimulants for athletes with ADHD are considered. The current article posits that a stimulant ban for athletes with ADHD does not necessarily facilitate fair play, ensure safety, or align with existing policies of large governing bodies. Instead, we recommend that stimulant medication be allowed in high-level sport, following proper diagnosis by a trained professional and a cardiac assessment to confirm no underlying heart conditions. Athletes with ADHD approved to use stimulant medication should be monitored by a health care professional, physically reevaluated and reassessed for ADHD as clinically appropriate and as indicated by relevant sports governing bodies. This performance and health perspective is consistent with that of multiple sport governing bodies who offer therapeutic use.


Asunto(s)
Atletas , Rendimiento Atlético , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Sustancias para Mejorar el Rendimiento/uso terapéutico , Deportes/ética , Rendimiento Atlético/ética , Humanos
12.
J Adolesc ; 63: 41-50, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29272766

RESUMEN

The current study examined perceived control over anxiety as a moderator in the relationship between AS and (1) alcohol use frequency and (2) binge drinking frequency among 80 community-recruited adolescents (Mage = 15.40; 40% female). Eighty-five percent of adolescents reported consuming an alcohol beverage, while 39.5% reported binge drinking. Results indicated significant interactions between AS and perceived control. More specifically, when perceived control was low, higher anxiety sensitivity was related to increased frequency of alcohol use days, but not with binge drinking days. Alternatively, when perceived control over anxiety was high, elevated anxiety sensitivity was associated with a decreased in binge drinking days, but not with alcohol use days. Findings suggest that influence of perceived control over anxiety may be another important, malleable factor that should be considered in future etiological and intervention-oriented work targeting anxiety sensitivity and alcohol misuse among adolescence.


Asunto(s)
Ansiedad/psicología , Consumo Excesivo de Bebidas Alcohólicas/psicología , Consumo de Alcohol en Menores/psicología , Adolescente , Consumo Excesivo de Bebidas Alcohólicas/epidemiología , Femenino , Humanos , Masculino , Percepción , Autoimagen , Autocontrol , Consumo de Alcohol en Menores/estadística & datos numéricos
13.
Sleep Med ; 30: 93-96, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28215271

RESUMEN

OBJECTIVE/BACKGROUND: Few adolescents report obtaining adequate amounts of sleep. Correlational studies have linked adolescent short sleep with driving crashes and sluggish cognitive tempo (SCT), a cluster of symptoms that include sluggishness and low persistence that are related to but distinct from inattention and sleepiness. The relationship between SCT and driving is understudied, and no study has experimentally examined the relationship between SCT and sleep. We examined the relationship between SCT and driving problems in a sample of chronically short-sleeping adolescents. We also examined whether experimentally extending sleep improved SCT and driving behaviors. PARTICIPANTS/METHODS: Licensed 16- to 18-year-old adolescents who regularly obtained five to seven hours of sleep completed a five-week at-home experimental protocol: a baseline week to determine typical sleep (TYP), followed in a counterbalanced order by two-week spans in which school-night bedtimes and rise times were (a) matched to TYP or (b) modified to extend (EXT) time in bed by 1.5 h/night. Sleep was monitored by actigraphy. Self- and parent-reported SCT and inattention and self-reported driving problems were recorded at baseline and following each condition. Of the 38 eligible participants who completed the baseline session, 24 completed all five weeks of the protocol. RESULTS: After controlling for inattention, only parent-reported SCT was significantly positively associated with self-reported purposeful driving violations at baseline. Adolescents reported lesser SCT during EXT than during TYP. Further, after controlling for inattention, participants who reported improvement in SCT demonstrated fewer driving problems during EXT than during TYP. CONCLUSIONS: Preliminary findings suggest that extending sleep in short-sleeping adolescents may help alleviate SCT symptoms and improve driving.


Asunto(s)
Atención , Conducción de Automóvil , Cognición , Privación de Sueño/complicaciones , Sueño , Adolescente , Femenino , Humanos , Masculino
14.
Nat Chem Biol ; 7(7): 445-52, 2011 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-21602812

RESUMEN

1,4-Butanediol (BDO) is an important commodity chemical used to manufacture over 2.5 million tons annually of valuable polymers, and it is currently produced exclusively through feedstocks derived from oil and natural gas. Herein we report what are to our knowledge the first direct biocatalytic routes to BDO from renewable carbohydrate feedstocks, leading to a strain of Escherichia coli capable of producing 18 g l(-1) of this highly reduced, non-natural chemical. A pathway-identification algorithm elucidated multiple pathways for the biosynthesis of BDO from common metabolic intermediates. Guided by a genome-scale metabolic model, we engineered the E. coli host to enhance anaerobic operation of the oxidative tricarboxylic acid cycle, thereby generating reducing power to drive the BDO pathway. The organism produced BDO from glucose, xylose, sucrose and biomass-derived mixed sugar streams. This work demonstrates a systems-based metabolic engineering approach to strain design and development that can enable new bioprocesses for commodity chemicals that are not naturally produced by living cells.


Asunto(s)
Butileno Glicoles/metabolismo , Escherichia coli/metabolismo , Organismos Modificados Genéticamente/metabolismo , Anaerobiosis , Vías Biosintéticas , Butileno Glicoles/química , Escherichia coli/enzimología , Escherichia coli/genética , Fermentación , Ingeniería Genética , Glucosa/metabolismo
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