Acurin A, a novel hybrid compound, biosynthesized by individually translated PKS- and NRPS-encoding genes in Aspergillus aculeatus.

This work presents the identification and proposed biosynthetic pathway for a compound of mixed polyketide-nonribosomal peptide origin that we named acurin A. The compound was isolated from an extract of the filamentous fungus Aspergillus aculeatus, and its core structure resemble that of the mycotoxin fusarin C produced by several Fusarium species. Based on bioinformatics in combination with RT-qPCR experiments and gene-deletion analysis, we identified a biosynthetic gene cluster (BGC) in A. aculeatus responsible for the biosynthesis of acurin A. Moreover, we were able to show that a polyketide synthase (PKS) and a nonribosomal peptide synthetase (NRPS) enzyme separately encoded by this BGC are responsible for the synthesis of the PK-NRP compound, acurin A, core structure. In comparison, the production of fusarin C is reported to be facilitated by a linked PKS-NRPS hybrid enzyme. Phylogenetic analyses suggest the PKS and NRPS in A. aculeatus resulted from a recent fission of an ancestral hybrid enzyme followed by gene duplication. In addition to the PKS- and NRPS-encoding genes of acurin A, we show that six other genes are influencing the biosynthesis including a regulatory transcription factor. Altogether, we have demonstrated the involvement of eight genes in the biosynthesis of acurin A, including an in-cluster transcription factor. This study highlights the biosynthetic capacity of A. aculeatus and serves as an example of how the CRISPR/Cas9 system can be exploited for the construction of fungal strains that can be readily engineered.

[Obesity in Danish hospitals--treatment in the year 2000]. / Adipositas på danske sygehuse--behandling anno 2000.

INTRODUCTION: Obesity is of increasing public health concern. The aim of the study was to investigate the treatment of obesity at Danish hospitals in the year 2000, and to compare the results with a similar study from 1987. MATERIALS AND METHODS: A questionnaire was sent to the heads of departments of internal medicine at all Danish hospitals where such departments exist (64). RESULTS: Ninety-one percent of the questionnaires were answered. Fewer hospitals (76%) in Denmark treated obesity in 2000 compared to 1987. About 1400 patients were referred, and the treatment of 500-900 patients was concluded yearly. Many departments reject patients when the primary diagnosis for referral is obesity, often because they lack resources or do not have the capacity. Except for university hospitals, obesity was more often treated on an outpatient basis in 2000 than in 1987. Apart from surgery, the same methods were used to treat obesity at the different types of hospitals. Instructions for treatment, long-term outpatient follow-up, quality assurance, evaluation of the treatment, and research in obesity are carried out to some degree at the university hospitals, and only to a small extent at other types of hospitals. DISCUSSION: Although obesity is becoming an increasing threat to public health, treatment at Danish hospitals has decreased over the last ten years, and in the year 2000 only a few per thousand obese patient were offered treatment by a hospital. Increased focus and resources, as well as development and research targeted specifically on the treatment of obesity are needed.

[Obesity in Danish hospitals--attitudes in the year 2000]. / Adipositas på danske sygehuse--holdninger anno 2000.

INTRODUCTION: The aim was to investigate the attitudes towards obesity of those responsible for the treatment at Danish hospitals. MATERIALS AND METHODS: A questionnaire was sent to the heads of departments of internal medicine at all Danish hospitals where such exist (n = 64). RESULTS: Eighty-nine per cent of the questionnaires were answered. Sixteen per cent believed that obesity is a self-imposed, life-style disease, and 56% answered "perhaps". 66% believed that obesity is a chronic condition or disease, and 32% thought that obese patients should be followed up life-long. Most believed that diseases would be prevented or improved, if obesity were treated, and 72% believed that it was possible to treat obesity. Thirty-five percent answered "perhaps" to whether it is worth the effort to treat obesity, as weight loss seldom lasts in the long term, and 25% answered "perhaps" to whether loss of weight in the obese incurs health risk. Fifty per cent believed that more resources were needed for the treatment of obesity, and that research in obesity should be given more attention, whereas only a few answered in the negative (6-9%). Thirty-three per cent believed that there was a need for public obesity clinics. Only 15% thought that Danish doctors are sufficiently trained to treat obesity, and only 9% answered "no" to whether better treatment of obesity required altered attitudes to obesity among Danish health care personnel. DISCUSSION: The heads of departments of internal medicine at Danish hospitals had different attitudes to obesity, but most believed that there is a need for altered attitudes, information, and training of Danish doctors and other health care personnel in the treatment of obesity.