Yeast engineering for the production of sclerol by lysophosphatidic acid synthase

By mutating and optimizing lysine pyrophosphate diol synthase, and combining this with strengthening the acetyl-CoA synthesis pathway and knocking out transcriptional regulators, yeast strains were modified to solve the problems of low yield and genetic instability of perillaldehyde, thus achieving high-yield perillaldehyde production.

CN121450628BActive Publication Date: 2026-04-07SICHUAN INGIA BIOSYNTHETIC CO LTD
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Patent Information

Application Number
CN202610010626.3
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2026-01-06
Publication Date
2026-04-07
Estimated Expiration
2046-01-06

AI Technical Summary

Technical Problem

In the existing technology, the biosynthetic yield of perillyl alcohol is low, and the expression of some Saccharomyces cerevisiae strains using free plasmids has genetic instability issues.

Method used

We mutated and optimized lysine pyrophosphate diol ester synthases (SsLPPs), and modified the salicylic acid synthetase of the salicylic acid-producing salicylic acid-producing bacteria by enhancing the synthesis pathways of acetyl-CoA, MVA, and GGPP, and knocking out some transcriptional regulators. Finally, we introduced the SsLPP mutant into the yeast genome.

Benefits of technology

It significantly increased the yield of perillyl alcohol, reaching 26.11 g/L in a 5 L fermenter, which is higher than the highest level recorded by existing technology and solved the problem of genetic instability.

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Abstract

The present application belongs to the field of biosynthesis, and particularly relates to pyrophosphate lyddane diol ester synthase and yeast engineering bacteria for producing sclareol. In order to solve the problem of generally low yield of sclareol biosynthesis in the prior art, the pyrophosphate lyddane diol ester synthase is mutated and optimized in the present application, and a SsLPPs mutant containing at least one mutation of D730L, D374L, N674L or G379M is obtained, and the mutant is used for sclareol synthesis. Meanwhile, in order to solve the problem of genetic instability existing in the expression of free plasmid in part of saccharomyces cerevisiae strains, the present application constructs a sclareol synthesis pathway in the yeast genome, and at the same time, the acetyl coenzyme A synthesis pathway, the MVA pathway and the sclareol synthesis pathway are strengthened, and part of the transcriptional repressor is knocked out, so that the bottom bacteria for synthesizing sclareol are modified. The yield in a 5 L fermenter reaches 26.11 g / L, and the yield is greatly improved compared with the prior art.
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