De Novo Design and Implementation of a Tandem Acyl Carrier Protein Domain in a Type I Modular Polyketide Synthase

Journal Article · Wed Oct 24 00:00:00 EDT 2018 · ACS Chemical Biology

DOI:https://doi.org/10.1021/acschembio.8b00896· OSTI ID:1490984

Wang, Zilong ^[1]; Bagde, Saket R. ^[2]; Zavala, Gerardo ^[2]; Matsui, Tsutomu ^[3]; Chen, Xi ^[4]; Kim, Chu -Young  ^[2]

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1. The Univ. of Texas at El Paso, El Paso, TX (United States); National Univ. of Singapore (Singapore)
2. The Univ. of Texas at El Paso, El Paso, TX (United States)
3. Stanford Univ., Menlo Park, CA (United States)
4. Northwest Univ., Xi'an (People's Republic of China)

During polyketide and fatty acid biosynthesis, the growing acyl chain is attached to the acyl carrier protein via a thioester linkage. The acyl carrier protein interacts with other enzymes that perform chain elongation and chain modification on the bound acyl chain. Most type I polyketide synthases and fatty acid synthases contain only one acyl carrier protein. However, polyunsaturated fatty acid synthases from deep-sea bacteria contain anywhere from two to nine acyl carrier proteins. Recent studies have shown that this tandem acyl carrier protein feature is responsible for the unusually high fatty acid production rate of deep-sea bacteria. To investigate if a similar strategy can be used to increase the production rate of type I polyketide synthases, a 3×ACP domain was rationally designed and genetically installed in module 6 of 6-deoxyerythronolide B synthase, which is a prototypical type I modular polyketide synthase that naturally harbors just one acyl carrier protein. As a result, this modification resulted in an ~2.5-fold increase in the total amount of polyketide produced in vitro, demonstrating that installing a tandem acyl carrier domain in a type I polyketide synthase is an effective strategy for enhancing the rate of polyketide natural product biosynthesis.

• Research Organization: SLAC National Accelerator Lab., Menlo Park, CA (United States)
• Sponsoring Organization: USDOE
• Grant/Contract Number: AC02-76SF00515; RL5GM118969; TL4GM118971; UL1GM118970
• OSTI ID: 1490984
• Journal Information: ACS Chemical Biology, Vol. 13, Issue 11; ISSN 1554-8929
• Publisher: American Chemical Society (ACS)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY