Microbial production of uracil by an isolated Methylobacterium sp. WJ4 using methanol

Highlights

• Uracil was produced from methanol by Methylobacterium sp. WJ4 for the first time.

• The effect of process parameters and methanol concentration were investigated.

• Methylobacterium sp. WJ4 produced uracil without genetic manipulation.

• Methylobacterium sp. WJ4 could be a candidate for uracil production from methanol.

Abstract

In this study, we report the production of uracil from methanol by an isolated methylotrophic bacterium, Methylobacterium sp. WJ4. The use of methanol as alternative carbon feedstock is attractive option in biotechnology. As a feedstock of biotechnological processes, methanol has distinct advantages over methane. This is not only due to physical and chemical considerations, but also to the properties of the pertinent organisms. Besides, with a wide array of biological activities and synthetic accessibility, uracil is considered as privileged structures in drug discovery. Uracil analogues have been applied to treatments of patients with cancer or viral infections. In this respect, it is meaningful to produce uracil using methanol. The effect of process parameters and methanol concentration for uracil production were investigated and optimized. Uracil production was remarkably increased to 5.76 mg g cell dry weight⁻¹ in optimized condition. The results were significant for further understanding of methylotrophic bacteria on uracil production.

Introduction

Methanol can be synthesized either from petrochemical or renewable resources, such as biogas [1]. The use of non-food competing carbon feedstock is an attractive option in biotechnology and one such alternative carbon feedstock is methanol. Methanol can be converted into a variety of products by biological processes [2]. Methylotrophic bacteria are of interest as biocatalysts for making useful chemicals and products by environmentally benign process from methanol [3]. Members of the genus Methylobacterium are ubiquitous in nature, detected in soil, freshwater and lake sediments, as well as on other solid surfaces and are facultative methylotrophic bacteria capable of either using one-carbon compounds, such as methanol, as their sole carbon and energy source via the serine pathway or using a variety of multi-carbon compounds [4], [5]. Methylobacterium has thus far been engineered to produce a variety of compounds using methanol as a feedstock [1]. The use of methylotrophs in bioprocesses has the added advantage that multi-step reactions for the synthesis of complex materials under ambient process conditions are feasible, compared to chemical processes [2].

Uracil has considered as privileged structure due to wide array of biological activities, synthetic accessibility and ability to confer drug like properties to the compound libraries appended on it at the N¹, N³, C⁵, and C⁶ positions [6]. Uracil analogues have been in clinical use for almost 50 years and have been applied in treatments of patients with cancer or viral infections, because of their anti-tumor and anti-viral properties [7]. They also possess herbicidal, insecticidal, and bactericidal activities [8], [9]. We found that uracil was produced when Methylobacterium sp. WJ4 was cultivated on methanol as a sole carbon source as shown in Scheme 1. Based on this result, we attempted to evaluate and optimize process parameters and methanol concentration. The results from this study were significant for further understanding of methylotrophic bacteria on uracil production.