Microbial production of multiple short-chain primary amines via retrobiosynthesis

Abstract

Bio-based production of many chemicals is not yet possible due to the unknown biosynthetic pathways. Here, we report a strategy combining retrobiosynthesis and precursor selection step to design biosynthetic pathways for multiple short-chain primary amines (SCPAs) that have a wide range of applications in chemical industries. Using direct precursors of 15 target SCPAs determined by the above strategy, Streptomyces viridifaciens vlmD encoding valine decarboxylase is examined as a proof-of-concept promiscuous enzyme both in vitro and in vivo for generating SCPAs from their precursors. Escherichia coli expressing the heterologous vlmD produces 10 SCPAs by feeding their direct precursors. Furthermore, metabolically engineered E. coli strains are developed to produce representative SCPAs from glucose, including the one producing 10.67 g L−1 of iso-butylamine by fed-batch culture. This study presents the strategy of systematically designing biosynthetic pathways for the production of a group of related chemicals as demonstrated by multiple SCPAs as examples.

Biosynthesis of cannabinoid precursor olivetolic acid in genetically engineered Yarrowia lipolytica

“…Microbial metabolic engineering is considered as the enabling technology to mitigate environmental concerns and address the scarcity of resource limitation challenges 7,8 . Compared to plantbased production system, microbes have a number of advantages, including less dependence on arable land or climate changes, ease of genetic manipulation and large-scale production, as well as robust growth and high conversion rate across a wide range of lowcost renewable raw materials 6,9 .…”

Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites

“…Primary amines are microbial metabolites that can be synthesized from amino acids through a one-step reaction mediated by bacterial decarboxylases ( 39 ). Based on whole-genome sequencing, M. morganii NWP135 encoded 18 predicted decarboxylases, including three decarboxylases (Peg1085, Peg1320, and Peg3098) that were partially homologous to a previously characterized valine decarboxylase from Streptomyces viridifaciens ( 39 ) (Fig. 4B and table S5).…”

Metabolic engineering of Escherichia coli for de novo production of 3-phenylpropanol via retrobiosynthesis approach

“…Retrobiosynthesis is an approach for biosynthetic pathway design from target molecules to cellular metabolites, using the biotransformation rules that present the rearrangement of atoms and bonds in enzymatic reactions [ 26 , 27 ]. With great potential in synthetic biology and metabolic engineering, retrobiosynthesis has been applied in the production of didanosine [ 28 ], 5‑aminolevulinic acid [ 29 ], and short-chain primary amines [ 30 ]. Furthermore, the current development of retrobiosynthesis tools for biosynthesis of valuable chemicals [ 27 , 31 , 32 ] provides a more feasible approach to rationally design a novel artificial pathway according to the available enzymatic reactions from databases, and then implement systems metabolic engineering strategies for efficient production of 3-phenylpropanol in microbes.…”