PreTKcat: A pre-trained representation learning and machine learning framework for predicting enzyme turnover number.

Journal: Computational biology and chemistry
PMID:

Abstract

The enzyme turnover number (k) is crucial for understanding enzyme kinetics and optimizing biotechnological processes. However, experimentally measured k values are limited due to the high cost and labor intensity of wet-lab measurements, necessitating robust computational methods. To address this issue, we propose PreTKcat, a framework that integrates pre-trained representation learning and machine learning to predict k values. PreTKcat utilizes the ProtT5 protein language model to encode enzyme sequences and the MolGNet molecular representation learning model to encode substrate molecular graphs. By integrating these representations, the ExtraTrees model is employed to predict k values. Additionally, PreTKcat accounts for the impact of temperature on k prediction. In addition, PreTKcat can also be used to predict enzyme-substrate affinity, i.e. km values. Comparative assessments with various state-of-the-art models highlight the superior performance of PreTKcat. PreTKcat serves as an effective tool for investigating enzyme kinetics, offering new perspectives for enzyme engineering and its industrial uses.

Authors

  • Yunxiang Cai
    Department of Clinical Laboratory, The First Affiliated Hospital of Huzhou University, The First People's Hospital of Huzhou City, Zhejiang Province, China.
  • Wenjuan Zhang
    Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
  • Zhuangzhuang Dou
    College of Artificial Intelligence, Tianjin University of Science and Technology, No. 9, 13th Street, Tianjin Economic-Technological Development Area, Tianjin, 300457, China.
  • Chao Wang
    College of Agriculture, Shanxi Agricultural University, Taigu, Shanxi, China.
  • Wenping Yu
    College of Artificial Intelligence, Tianjin University of Science and Technology, No. 9, 13th Street, Tianjin Economic-Technological Development Area, Tianjin, 300457, China.
  • Lin Wang
    Department of Engineering Mechanics, Tsinghua University, Beijing 100084, China.