Liu et al. Bioresour. Bioprocess. (2018) 5:23 https://doi.org/10.1186/s40643-018-0209-5 RESEARCH 2-Hydroxy-4-(3′-oxo-3′H-benzofura n-2′-yliden)but-2-enoic acid biosynthesis from dibenzofuran using lateral dioxygenation in a Pseudomonas putida strain B6-2 (DSM 28064) Xin Liu † , Weiwei Wang † , Haiyang Hu, Xinyu Lu, Lige Zhang, Ping Xu and Hongzhi Tang * Abstract Background: Benzofuran and its derivatives contain central pharmacophores and are important structures in medicinal chemistry. Chemical synthesis of benzofuran rings often requires expensive catalysts and stringent opera- tional conditions. Biosynthesis is recognized as a promising way to save energy and produce valuable compounds. Dioxin biodegradation pathways can form several benzofuran derivatives, and these pathways may be a better choice for further synthesis of important biological compounds. 2-Hydroxy-4-(3′-oxo-3′H-benzofuran-2′-yliden)but-2-enoic acid (HOBB), a benzofuran derivative, can be biosynthesized from dibenzofuran (DBF) through co-metabolic degrada- tion in a lateral dioxygenation pathway. Results: Efficient biosynthesis of HOBB was observed using whole cells of Pseudomonas putida strain B6-2. After cul- tivation in LB medium containing biphenyl, the cells were suspended to an OD 600 of 5 to conduct biosynthesis in the presence of 0.5-mM DBF at pH 7 for 8 h. The bacterial cells were used twice to degrade approximately 0.70-mM DBF, and in batch process, accumulated about 0.29-mM HOBB. HOBB could be easily purified from the reaction with ethyl acetate using the neutral-acid extraction method, and 13.58 ± 0.31 mg of HOBB was obtained from 22.49 ± 0.74-mg DBF with an overall production yield of 60.4% (w/w). The product HOBB, which is a yellow powder, could be detected and identified by LC–MS, GC–MS, and NMR. Conclusions: In this study, a new biological route was developed to produce HOBB from DBF using whole cells of P. putida B6-2 (DSM 28064). The biosynthesis of HOBB may contribute to studies of the DBF lateral pathway and provide a new green route for synthesizing benzofuran derivatives with pharmacological activities. Keywords: Biosynthesize, Pseudomonas putida, Lateral dioxygenation, HOBB © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Open Access *Correspondence: tanghongzhi@sjtu.edu.cn † Xin Liu and Weiwei Wang have contributed equally to this work State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China Background Many natural products with biological activities are ben- zofuran heterocycles (Nevagi et al. 2015; Yeung 2012). Benzofuran and its derivatives are central pharmacoph- ores and important structures in medicinal chemistry (Fig. 1a) because of their broad spectra of pharmacologi- cal activities (Khanam and Shamsuzzaman 2015). Tese products contain mono and fused benzofuran rings in conjunction with other heterocycle compounds (Nevagi et al. 2015). For example, 4-hydroxy-3-methyl-6-phe- nylbenzofuran-2-carboxylic acid ethyl ester was reported as an anti-tumor agent (Hayakawa et al. 2004a, b), a series of imidazopyridinylbenzofurans have been identi- fed as potent, non-peptide antagonists of angiotensin II (Judd et al. 1994), and other benzofuran derivatives