Solar Fuels and Chemicals: Engineering Bacterial Platform for the Production of Long-Chain Hydrocarbons from Carbon Dioxide and Electricity

Microbial synthesis of long-chain hydrocarbons is considered a promising method for the production of drop-in replacements for the currently utilized fossil fuels and chemicals. In a sustainable future, the carbon and energy required for the synthesis of these compounds should be ultimately derived from carbon dioxide (CO2) and the sun. Additionally, the produced compounds should be of similar or higher quality than the fossil counterparts they aim to replace, enabling their utilization directly in the existing processes and infrastructure. Solar energy can be efficiently captured by man-made devices, and converted to electricity. Some microbes are capable of utilizing the electrical energy for the reduction of CO2 into organic molecules, while other microbes hold the potential for the specific production of long-chain hydrocarbons. However, these two processes are difficult to achieve efficiently in any single organism, owing to their contrasting requirements for the host cells’ metabolism.In this study, a two-stage bacterial platform for the production of long-chain hydrocarbons from carbon dioxide was developed. In the first stage, acetogenic bacteria produce acetate from carbon dioxide and electricity as the sole sources of carbon and energy. In the second stage, the acetate is converted to long-chain hydrocarbons by a second bacterium, Acinetobacter baylyi. The platform is modular in nature, and different acetate-producing and -consuming processes can be combined. The final product can be determined and the production enhanced by genetically engineering A. baylyi.Fatty aldehydes are specific intermediates in the biosynthesis of wax esters and alkanes. Fatty acyl-CoA reductases (FARs) are key enzymes in the production of fatty aldehydes. The natural fatty aldehyde production of A. baylyi was improved by overexpressing either native or heterologous FARs. The overexpression led to increased fatty aldehyde production, and enabled more efficient wax ester or alkane production, depending on the downstream pathway utilized. For the wax ester production, the native wax ester production pathway of A. baylyi, combined with the overexpression of the native FAR or a previously uncharacterized, putative reductase from Nevskia ramosa, was employed. The overexpression of either of these reductases led to increased wax ester production, resulting in the highest wax ester titers reported thus far for microbial production systems. A. baylyi does not naturally produce alkanes, but the expression of a two-step cyanobacterial pathway consisting of aldehyde- and alkane producing enzymes led to alkane synthesis. Furthermore, the natural ability of A. baylyi for alkane degradation was removed, thereby converting the natural alkane degrader into alkane producer.The development of efficient production strains by metabolic engineering is restricted by the lack of sensitive and specific measurement methods for the target compounds. Intracellular biosensors may offer convenient means for high-throughput screening and optimization of the production strains. In order to study heterologous alkane biosynthesis in A. baylyi, an in vivo alkane biosensor working on two levels was developed. First, a gene encoding the green fluorescent protein (GFP) was placed under an alkane-inducible promoter, linking the alkane production to the expression of GFP. The second level is provided by a constantly expressed bacterial luciferase LuxAB, which utilizes the fatty aldehyde intermediate as a substrate in a reaction that produces visible light. Thus, the production of fatty aldehydes can be monitored with the luminescence signal. The two-level configuration of the sensor enabled the screening of different alkane-producing pathways, and the optimization of the expression levels of the pathway enzymes in order to improve the alkane biosynthesis in A. baylyi.In summary, the production of wax esters from CO2 and electricity, as well as long-chain alkanes from CO2 and H2 were demonstrated with the two-stage bacterial platform. In addition, heterologous alkane biosynthesis was demonstrated in A. baylyi, and the natural wax ester production of A. baylyi was improved by metabolic engineering. Even though the platform holds potential for the sustainable production of drop-in fuels and chemicals, significant improvements in the production efficiency are required before the potential can be realized

Production of long chain alkyl esters from carbon dioxide and electricity by a two-stage bacterial process

Microbial electrosynthesis (MES) is a promising technology for the reduction of carbon dioxide into value-added multicarbon molecules. In order to broaden the product profile of MES processes, we developed a two-stage process for microbial conversion of carbon dioxide and electricity into long chain alkyl esters. In the first stage, the carbon dioxide is reduced to organic compounds, mainly acetate, in a MES process by Sporomusa ovata. In the second stage, the liquid end-products of the MES process are converted to the final product by a second microorganism, Acinetobacter baylyi in an aerobic bioprocess. In this proof-of-principle study, we demonstrate for the first time the bacterial production of long alkyl esters (wax esters) from carbon dioxide and electricity as the sole sources of carbon and energy. The process holds potential for the efficient production of carbon-neutral chemicals or biofuels.acceptedVersionPeer reviewe

Kasvua digitaalisesta turvallisuudesta : Tiekartta 2019–2030

Digitaalisen turvallisuuden kasvun tiekartan tavoitteena on edistää digitaaliseen turvallisuuteen ja osaamiseen liittyvää yritysvetoista kehitystä, kasvua ja kansainvälistymistä yritysten, julkisen sektorin ja tutkimuslaitosten yhteistyönä. Raportissa esitetään digitaalisen turvallisuuden alan yhteinen tavoitetila ja tulevaisuuskuva vuodelle 2030, kuvataan alan osaaminen ja toimintaympäristö, määritetään teemakohtaiset visiot vuodelle 2030 ja keskeiset välitavoitteet vuosille 2021 ja 2025. Tiekartta voi toimia käytännön työkaluna suunniteltaessa uusia kyberturvallisuusosaamista vahvistavia politiikkatoimia ja niiden toteutusta sekä mahdollistettaessa toimijoiden kasvupolkuja esimerkiksi erilaisten ekosysteemien ja kiihdyttämöjen kautta. Raportin on tilannut ja sitä on ohjannut työ- ja elinkeinoministeriö. Ohjausryhmätyöhön ovat lisäksi osallistuneet liikenne- ja viestintäministeriö, opetus- ja kulttuuriministeriö, Huoltovarmuuskeskus ja Business Finland. Tiekartan valmistelutyön tarkoituksena on ollut tunnistaa tärkeimmät sidosryhmät ja muodostaa kansallinen viitekehys digitaalisen turvallisuuden tutkimus-, kehitys- ja innovaatiotoiminnan (TKI-toiminnan) investointien suuntaamiseksi. Lisäksi valmistelutyössä tunnistettiin toimenpiteitä, joilla voidaan vahvistaa Suomen asemaa kansainvälisesti tunnettuna digitaalisen turvallisuuden tutkimuksen, innovaatiotoiminnan, investointien ja uuden liiketoiminnan edelläkävijänä. Valmistelutyön löydökset ja toimenpidesuositukset tarjoavat pohjan kyberturvallisuusosaamisen ja siihen tukeutuvan liiketoiminnan kasvua edistävän ohjelmatoiminnan käynnistämiselle ja jatkotoimenpiteiden suunnittelulle ja toteutukselle

Association of Chlamydia trachomatis infection with cervical atypia in adolescent women with short-term or long-term use of oral contraceptives : a longitudinal study in HPV vaccinated women

Objective We assessed the relationship between Chlamydia trachomatis infection, duration of oral contraceptive (OC) use and cervical atypia among young adult Finnish women. Design A longitudinal study. Setting and participants Women who were included in this study participated in a community-randomised trial on the effectiveness of human papillomavirus (HPV) vaccination and C. trachomatis screening at ages 18.5 and 22 years in Finland. They completed questionnaires on both visits about sexual behaviours. The cytology test results at age 18.5 and 22 years were also available for those women. The total number of participants in this study at 18.5 years of age were 11 701 and at 22 years of age were 6618. Main outcome measure ORs with 95% CIs using univariable and multivariable logistic regression were used to assess the association between C. trachomatis infection, duration of OC and squamous intraepithelial lesions (SIL). Results There were 940 cytological SIL cases at the first screening visit and 129 cytological SIL cases at the second screening visit. Among the 22 years old, more than fourfold adjusted risk of SIL was associated with C. trachomatis positivity. The HPV16/18, condom use, smoking and number of sexual partners adjusted joint effect of prolonged OC use and C. trachomatis was significantly increased (OR 4.7, 95% CI 1.7 to 12.8) in the 22-year-old women. This observed joint effect was 1.6 times higher than expected on a multiplicative scale. On additive scale, the observed relative excess risk from interaction was 1.8. Conclusion The risk of SIL in HPV vaccinated women is significantly increased if they are C. trachomatis positive and have used OC for 5 or more years. The biological basis may be lack of condom facilitated protection against sexually transmitted diseases.Peer reviewe

Arthroscopic Bankart versus open Latarjet as a primary operative treatment for traumatic anteroinferior instability in young males : a randomised controlled trial with 2-year follow-up

Objectives To compare the success rates of arthroscopic Bankart and open Latarjet procedure in the treatment of traumatic shoulder instability in young males. Design Multicentre randomised controlled trial. Setting Orthopaedic departments in eight public hospitals in Finland. Participants 122 young males, mean age 21 years (range 16-25 years) with traumatic shoulder anteroinferior instability were randomised. Interventions Arthroscopic Bankart (group B) or open Latarjet (group L) procedure. Main outcome measures The primary outcome measure was the reported recurrence of instability, that is, dislocation at 2-year follow-up. The secondary outcome measures included clinical apprehension, sports activity level, the Western Ontario Shoulder Instability Index, the pain Visual Analogue Scale, the Oxford Shoulder Instability Score, the Constant Score and the Subjective Shoulder Value scores and the progression of osteoarthritic changes in plain films and MRI. Results 91 patients were available for analyses at 2-year follow-up (drop-out rate 25%). There were 10 (21%) patients with redislocations in group B and 1 (2%) in group L, p=0.006. One (9%) patient in group B and five (56%) patients in group L returned to their previous top level of competitive sports (p=0.004) at follow-up. There was no statistically significant between group differences in any of the other secondary outcome measures. Conclusions Arthroscopic Bankart operation carries a significant risk for short-term postoperative redislocations compared with open Latarjet operation, in the treatment of traumatic anteroinferior instability in young males. Patients should be counselled accordingly before deciding the surgical treatment.Peer reviewe

Transient Changes in Serum CEA, CA19-9, CRP, YKL-40, and IL-6 during Adjuvant Chemotherapy and Survival of Patients with Colorectal Cancer

Serum carcinoembryonic antigen (CEA) is frequently monitored to detect colorectal cancer (CRC) recurrence after surgery. The clinical significance of transiently increased CEA during adjuvant chemotherapy is poorly understood. Serum CEA, CA19-9, CRP, YKL-40, and IL-6 were measured before, during, and after adjuvant 5-fluorouracil-based chemotherapy in the randomised LIPSYT study population. The biomarker kinetic patterns were classified into three groups: no increase, a transient increase (≥10% increase followed by a decrease), and a persistent increase during the adjuvant treatment, and the associations of these patterns with disease free-survival (DFS) and overall survival (OS) were investigated by using Cox regression analyses. The findings were validated in two single-centre cohorts that received modern adjuvant chemotherapy. A transient increase in CEA occurred in about a half of the patients during chemotherapy, in all the cohorts. The patients with a transient increase had a roughly similar DFS and OS to the patients with no increase, and a more favourable survival compared to the patients with a persistent increase. In the LIPSYT cohort, the hazard ratio was 0.21 for DFS (CI95% 0.07–0.66) and 0.24 for OS (CI95% 0.08–0.76). Transient increases in CA19-9 and YKL-40 tended to be associated with a favourable survival. A transient increase in CEA during adjuvant chemotherapy is associated with a favourable survival when compared with a persistent increase