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Production of semi-biosynthetic nepetalactone in yeast.

ABSTRACT: Microbial-based production of natural products provides a promising alternative to synthetic production and isolation from the native producer. The recently discovered NEPS1 cyclase/oxidase completes the biosynthetic pathway to nepetalactone, a biologically relevant iridoid known as both an insect repellent and cat attractant. In this work, we employ yeast-based whole-cell biocatalysis to produce semi-biosynthetic nepetalactone from a low-cost precursor via a four-step enzymatic process. The dependence of product yield on bioprocess parameters ranging from induction of gene expression to substrate loading was investigated. Subsequent factorial design and response surface methodology optimization approach enabled a 5.8-fold increase in nepetalactone titer to 153 mg/L. Our study provides insights into strategies for operating plasmid-based bioconversion of a fed substrate and sets the stage for scalable, microbial synthesis of nepetalactone.

SUBMITTER: Billingsley JM

PROVIDER: S-EPMC6927397 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Production of semi-biosynthetic nepetalactone in yeast.

Billingsley John M JM Anguiano Jose L JL Tang Yi Y

Journal of industrial microbiology & biotechnology 20190605 9-10

Microbial-based production of natural products provides a promising alternative to synthetic production and isolation from the native producer. The recently discovered NEPS1 cyclase/oxidase completes the biosynthetic pathway to nepetalactone, a biologically relevant iridoid known as both an insect repellent and cat attractant. In this work, we employ yeast-based whole-cell biocatalysis to produce semi-biosynthetic nepetalactone from a low-cost precursor via a four-step enzymatic process. The dep ...[more]

PMID: 31165969

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Project description:Every protein has a biosynthetic cost to the cell based on the synthesis of its constituent amino acids. In order to optimise growth and reproduction, natural selection is expected, where possible, to favour the use of proteins whose constituents are cheaper to produce, as reduced biosynthetic cost may confer a fitness advantage to the organism. Quantifying the cost of amino acid biosynthesis presents challenges, since energetic requirements may change across different cellular and environmental conditions. We developed a systems biology approach to estimate the cost of amino acid synthesis based on genome-scale metabolic models and investigated the effects of the cost of amino acid synthesis on Saccharomyces cerevisiae gene expression and protein evolution. First, we used our two new and six previously reported measures of amino acid cost in conjunction with codon usage bias, tRNA gene number and atomic composition to identify which of these factors best predict transcript and protein levels. Second, we compared amino acid cost with rates of amino acid substitution across four species in the genus Saccharomyces. Regardless of which cost measure is used, amino acid biosynthetic cost is weakly associated with transcript and protein levels. In contrast, we find that biosynthetic cost and amino acid substitution rates show a negative correlation, but for only a subset of cost measures. In the economy of the yeast cell, we find that the cost of amino acid synthesis plays a limited role in shaping transcript and protein expression levels compared to that of translational optimisation. Biosynthetic cost does, however, appear to affect rates of amino acid evolution in Saccharomyces, suggesting that expensive amino acids may only be used when they have specific structural or functional roles in protein sequences. However, as there appears to be no single currency to compute the cost of amino acid synthesis across all cellular and environmental conditions, we conclude that a systems approach is necessary to unravel the full effects of amino acid biosynthetic cost in complex biological systems.

Dataset Information

Production of semi-biosynthetic nepetalactone in yeast.

Publications

Production of semi-biosynthetic nepetalactone in yeast.

Similar Datasets

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